TCR/pMHC interaction: phenotypic model for an unsolved enigma

TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Jesus Galvez [verfasserIn] Juan J. Galvez [verfasserIn] Pilar Garcia-Peñarrubia [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2016

Schlagwörter:	Kinetic proofreading TCR activation stabilization and destabilization of TCR/pMHC complexes dissociation and propagation rate constants activation chain

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 7(2016)
Übergeordnetes Werk:	volume:7 ; year:2016

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2016.00467

Katalog-ID:	DOAJ075333007

Internformat


LEADER	01000caa a22002652 4500
001	DOAJ075333007
003	DE-627
005	20230309133509.0
007	cr uuu---uuuuu
008	230228s2016 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.3389/fimmu.2016.00467 \|2 doi
035			\|a (DE-627)DOAJ075333007
035			\|a (DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
050		0	\|a RC581-607
100	0		\|a Jesus Galvez \|e verfasserin \|4 aut
245	1	0	\|a TCR/pMHC interaction: phenotypic model for an unsolved enigma
264		1	\|c 2016
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed.
650		4	\|a Kinetic proofreading
650		4	\|a TCR activation
650		4	\|a stabilization and destabilization of TCR/pMHC complexes
650		4	\|a dissociation and propagation rate constants
650		4	\|a activation chain
653		0	\|a Immunologic diseases. Allergy
700	0		\|a Juan J. Galvez \|e verfasserin \|4 aut
700	0		\|a Juan J. Galvez \|e verfasserin \|4 aut
700	0		\|a Pilar Garcia-Peñarrubia \|e verfasserin \|4 aut
773	0	8	\|i In \|t Frontiers in Immunology \|d Frontiers Media S.A., 2011 \|g 7(2016) \|w (DE-627)657998354 \|w (DE-600)2606827-8 \|x 16643224 \|7 nnns
773	1	8	\|g volume:7 \|g year:2016
856	4	0	\|u https://doi.org/10.3389/fimmu.2016.00467 \|z kostenfrei
856	4	0	\|u https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60 \|z kostenfrei
856	4	0	\|u http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/1664-3224 \|y Journal toc \|z kostenfrei
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_DOAJ
912			\|a GBV_ILN_11
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 7 \|j 2016

Indexfelder

author_variant	j g jg j j g jjg j j g jjg p g p pgp
matchkey_str	article:16643224:2016----::cphitrcinhntpcoefrn
hierarchy_sort_str	2016
callnumber-subject-code	RC
publishDate	2016
allfields	10.3389/fimmu.2016.00467 doi (DE-627)DOAJ075333007 (DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60 DE-627 ger DE-627 rakwb eng RC581-607 Jesus Galvez verfasserin aut TCR/pMHC interaction: phenotypic model for an unsolved enigma 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed. Kinetic proofreading TCR activation stabilization and destabilization of TCR/pMHC complexes dissociation and propagation rate constants activation chain Immunologic diseases. Allergy Juan J. Galvez verfasserin aut Juan J. Galvez verfasserin aut Pilar Garcia-Peñarrubia verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 7(2016) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:7 year:2016 https://doi.org/10.3389/fimmu.2016.00467 kostenfrei https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2016
spelling	10.3389/fimmu.2016.00467 doi (DE-627)DOAJ075333007 (DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60 DE-627 ger DE-627 rakwb eng RC581-607 Jesus Galvez verfasserin aut TCR/pMHC interaction: phenotypic model for an unsolved enigma 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed. Kinetic proofreading TCR activation stabilization and destabilization of TCR/pMHC complexes dissociation and propagation rate constants activation chain Immunologic diseases. Allergy Juan J. Galvez verfasserin aut Juan J. Galvez verfasserin aut Pilar Garcia-Peñarrubia verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 7(2016) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:7 year:2016 https://doi.org/10.3389/fimmu.2016.00467 kostenfrei https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2016
allfields_unstemmed	10.3389/fimmu.2016.00467 doi (DE-627)DOAJ075333007 (DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60 DE-627 ger DE-627 rakwb eng RC581-607 Jesus Galvez verfasserin aut TCR/pMHC interaction: phenotypic model for an unsolved enigma 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed. Kinetic proofreading TCR activation stabilization and destabilization of TCR/pMHC complexes dissociation and propagation rate constants activation chain Immunologic diseases. Allergy Juan J. Galvez verfasserin aut Juan J. Galvez verfasserin aut Pilar Garcia-Peñarrubia verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 7(2016) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:7 year:2016 https://doi.org/10.3389/fimmu.2016.00467 kostenfrei https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2016
allfieldsGer	10.3389/fimmu.2016.00467 doi (DE-627)DOAJ075333007 (DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60 DE-627 ger DE-627 rakwb eng RC581-607 Jesus Galvez verfasserin aut TCR/pMHC interaction: phenotypic model for an unsolved enigma 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed. Kinetic proofreading TCR activation stabilization and destabilization of TCR/pMHC complexes dissociation and propagation rate constants activation chain Immunologic diseases. Allergy Juan J. Galvez verfasserin aut Juan J. Galvez verfasserin aut Pilar Garcia-Peñarrubia verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 7(2016) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:7 year:2016 https://doi.org/10.3389/fimmu.2016.00467 kostenfrei https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2016
allfieldsSound	10.3389/fimmu.2016.00467 doi (DE-627)DOAJ075333007 (DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60 DE-627 ger DE-627 rakwb eng RC581-607 Jesus Galvez verfasserin aut TCR/pMHC interaction: phenotypic model for an unsolved enigma 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed. Kinetic proofreading TCR activation stabilization and destabilization of TCR/pMHC complexes dissociation and propagation rate constants activation chain Immunologic diseases. Allergy Juan J. Galvez verfasserin aut Juan J. Galvez verfasserin aut Pilar Garcia-Peñarrubia verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 7(2016) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:7 year:2016 https://doi.org/10.3389/fimmu.2016.00467 kostenfrei https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2016
language	English
source	In Frontiers in Immunology 7(2016) volume:7 year:2016
sourceStr	In Frontiers in Immunology 7(2016) volume:7 year:2016
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Kinetic proofreading TCR activation stabilization and destabilization of TCR/pMHC complexes dissociation and propagation rate constants activation chain Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Jesus Galvez @@aut@@ Juan J. Galvez @@aut@@ Pilar Garcia-Peñarrubia @@aut@@
publishDateDaySort_date	2016-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ075333007
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ075333007</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309133509.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2016 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2016.00467</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ075333007</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Jesus Galvez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">TCR/pMHC interaction: phenotypic model for an unsolved enigma</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2016</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kinetic proofreading</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">TCR activation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">stabilization and destabilization of TCR/pMHC complexes</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">dissociation and propagation rate constants</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">activation chain</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. Allergy</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan J. Galvez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan J. Galvez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pilar Garcia-Peñarrubia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Immunology</subfield><subfield code="d">Frontiers Media S.A., 2011</subfield><subfield code="g">7(2016)</subfield><subfield code="w">(DE-627)657998354</subfield><subfield code="w">(DE-600)2606827-8</subfield><subfield code="x">16643224</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:7</subfield><subfield code="g">year:2016</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3389/fimmu.2016.00467</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1664-3224</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">7</subfield><subfield code="j">2016</subfield></datafield></record></collection>
callnumber-first	R - Medicine
author	Jesus Galvez
spellingShingle	Jesus Galvez misc RC581-607 misc Kinetic proofreading misc TCR activation misc stabilization and destabilization of TCR/pMHC complexes misc dissociation and propagation rate constants misc activation chain misc Immunologic diseases. Allergy TCR/pMHC interaction: phenotypic model for an unsolved enigma
authorStr	Jesus Galvez
ppnlink_with_tag_str_mv	@@773@@(DE-627)657998354
format	electronic Article
delete_txt_mv	keep
author_role	aut aut aut aut
collection	DOAJ
remote_str	true
callnumber-label	RC581-607
illustrated	Not Illustrated
issn	16643224
topic_title	RC581-607 TCR/pMHC interaction: phenotypic model for an unsolved enigma Kinetic proofreading TCR activation stabilization and destabilization of TCR/pMHC complexes dissociation and propagation rate constants activation chain
topic	misc RC581-607 misc Kinetic proofreading misc TCR activation misc stabilization and destabilization of TCR/pMHC complexes misc dissociation and propagation rate constants misc activation chain misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc Kinetic proofreading misc TCR activation misc stabilization and destabilization of TCR/pMHC complexes misc dissociation and propagation rate constants misc activation chain misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc Kinetic proofreading misc TCR activation misc stabilization and destabilization of TCR/pMHC complexes misc dissociation and propagation rate constants misc activation chain misc Immunologic diseases. Allergy
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	Frontiers in Immunology
hierarchy_parent_id	657998354
hierarchy_top_title	Frontiers in Immunology
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)657998354 (DE-600)2606827-8
title	TCR/pMHC interaction: phenotypic model for an unsolved enigma
ctrlnum	(DE-627)DOAJ075333007 (DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60
title_full	TCR/pMHC interaction: phenotypic model for an unsolved enigma
author_sort	Jesus Galvez
journal	Frontiers in Immunology
journalStr	Frontiers in Immunology
callnumber-first-code	R
lang_code	eng
isOA_bool	true
recordtype	marc
publishDateSort	2016
contenttype_str_mv	txt
author_browse	Jesus Galvez Juan J. Galvez Pilar Garcia-Peñarrubia
container_volume	7
class	RC581-607
format_se	Elektronische Aufsätze
author-letter	Jesus Galvez
doi_str_mv	10.3389/fimmu.2016.00467
author2-role	verfasserin
title_sort	tcr/pmhc interaction: phenotypic model for an unsolved enigma
callnumber	RC581-607
title_auth	TCR/pMHC interaction: phenotypic model for an unsolved enigma
abstract	TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed.
abstractGer	TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed.
abstract_unstemmed	TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
title_short	TCR/pMHC interaction: phenotypic model for an unsolved enigma
url	https://doi.org/10.3389/fimmu.2016.00467 https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60 http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full https://doaj.org/toc/1664-3224
remote_bool	true
author2	Juan J. Galvez Pilar Garcia-Peñarrubia
author2Str	Juan J. Galvez Pilar Garcia-Peñarrubia
ppnlink	657998354
callnumber-subject	RC - Internal Medicine
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.3389/fimmu.2016.00467
callnumber-a	RC581-607
up_date	2024-07-03T14:18:13.794Z
_version_	1803567805288677376
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ075333007</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309133509.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2016 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2016.00467</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ075333007</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJcc7fe5263f414b9dbc6eb526e5267b60</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Jesus Galvez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">TCR/pMHC interaction: phenotypic model for an unsolved enigma</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2016</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">TCR-pMHC interaction is the keystone of the adaptive immune response.This process exhibits animpressive capacity of speed, sensitivity and discrimination thatallows to detect foreign pMHCs at very low concentration amongmuch more abundant self-pMHC ligands.However, and despite over three decades of intensive research,the mechanisms by which this remarkablediscrimination and sensitivity is attained remain controversial.In kinetic proofreading mechanisms (KPR)an increase of specificity occurs by reducing thesensitivity. To overcome this difficulty more elaborate modelsincluding feedback processes or induced rebinding have beenincorporated into the KPR scheme.Here a new approach based on the assumptionthat the proofreading chain behaves differently forforeign and self pMHCs has been integrated into aphenotypic model in which the complexes responsible for T cell activationstabilize (for foreign peptides), or weaken (for foreign peptides),resulting in a dramatic increase in sensitivity andspecificity. Stabilization and destabilizationof complexes may be caused by conformational changes, rebinding, orany other process leading to variations in the dissociation rateconstants of the complexes transmitting the activation. Thenumerical solution and the analytical expression for the steadystate response as a function of k off (i)(i=0,1,..,N, where C0, C1,..,CN are the complexes inthe proofreading chain) are provided. The activation chain speedsup and larger increases in sensitivity and discrimination areobtained if the rate of activation along the proofreading chainincreases for foreign pMHCs and decreases for self ligands.Experimental implications and comparison with current models are discussed.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kinetic proofreading</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">TCR activation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">stabilization and destabilization of TCR/pMHC complexes</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">dissociation and propagation rate constants</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">activation chain</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. Allergy</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan J. Galvez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Juan J. Galvez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pilar Garcia-Peñarrubia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Frontiers in Immunology</subfield><subfield code="d">Frontiers Media S.A., 2011</subfield><subfield code="g">7(2016)</subfield><subfield code="w">(DE-627)657998354</subfield><subfield code="w">(DE-600)2606827-8</subfield><subfield code="x">16643224</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:7</subfield><subfield code="g">year:2016</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3389/fimmu.2016.00467</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/cc7fe5263f414b9dbc6eb526e5267b60</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00467/full</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1664-3224</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">7</subfield><subfield code="j">2016</subfield></datafield></record></collection>
score	7.4008694

Nicht das Richtige dabei?

Schreiben Sie uns!

TCR/pMHC interaction: phenotypic model for an unsolved enigma

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?