Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation

<p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p< Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Salentijn Elma MJ [verfasserIn] Mitea D [verfasserIn] Goryunova Svetlana V [verfasserIn] van der Meer Ingrid M [verfasserIn] Padioleau Ismael [verfasserIn] Gilissen Luud JWJ [verfasserIn] Koning Frits [verfasserIn] Smulders Marinus JM [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2012

Schlagwörter:	Wheat Gluten γ-gliadins Celiac disease T-cell epitopes

Übergeordnetes Werk:	In: BMC Genomics - BMC, 2003, 13(2012), 1, p 277
Übergeordnetes Werk:	volume:13 ; year:2012 ; number:1, p 277

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/1471-2164-13-277

Katalog-ID:	DOAJ065167635

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650		4	\|a Gluten
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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_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_95
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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_702
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2006
912			\|a GBV_ILN_2008
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2010
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2031
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912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2056
912			\|a GBV_ILN_2057
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2190
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 13 \|j 2012 \|e 1, p 277

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author_variant	s e m sem m d md g s v gsv v d m i m vdmim p i pi g l j glj k f kf s m j smj
matchkey_str	article:14712164:2012----::eiciestelptpsrmamgidnimnratvtdpnsnhgnmooiitasrpf
hierarchy_sort_str	2012
callnumber-subject-code	TP
publishDate	2012
allfields	10.1186/1471-2164-13-277 doi (DE-627)DOAJ065167635 (DE-599)DOAJ1c7ef484b2b74b9d87dcc960ac63e3cd DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Salentijn Elma MJ verfasserin aut Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p< Wheat Gluten γ-gliadins Celiac disease T-cell epitopes Biotechnology Genetics Mitea D verfasserin aut Goryunova Svetlana V verfasserin aut van der Meer Ingrid M verfasserin aut Padioleau Ismael verfasserin aut Gilissen Luud JWJ verfasserin aut Koning Frits verfasserin aut Smulders Marinus JM verfasserin aut In BMC Genomics BMC, 2003 13(2012), 1, p 277 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:13 year:2012 number:1, p 277 https://doi.org/10.1186/1471-2164-13-277 kostenfrei https://doaj.org/article/1c7ef484b2b74b9d87dcc960ac63e3cd kostenfrei http://www.biomedcentral.com/1471-2164/13/277 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 13 2012 1, p 277
spelling	10.1186/1471-2164-13-277 doi (DE-627)DOAJ065167635 (DE-599)DOAJ1c7ef484b2b74b9d87dcc960ac63e3cd DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Salentijn Elma MJ verfasserin aut Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p< Wheat Gluten γ-gliadins Celiac disease T-cell epitopes Biotechnology Genetics Mitea D verfasserin aut Goryunova Svetlana V verfasserin aut van der Meer Ingrid M verfasserin aut Padioleau Ismael verfasserin aut Gilissen Luud JWJ verfasserin aut Koning Frits verfasserin aut Smulders Marinus JM verfasserin aut In BMC Genomics BMC, 2003 13(2012), 1, p 277 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:13 year:2012 number:1, p 277 https://doi.org/10.1186/1471-2164-13-277 kostenfrei https://doaj.org/article/1c7ef484b2b74b9d87dcc960ac63e3cd kostenfrei http://www.biomedcentral.com/1471-2164/13/277 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 13 2012 1, p 277
allfields_unstemmed	10.1186/1471-2164-13-277 doi (DE-627)DOAJ065167635 (DE-599)DOAJ1c7ef484b2b74b9d87dcc960ac63e3cd DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Salentijn Elma MJ verfasserin aut Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p< Wheat Gluten γ-gliadins Celiac disease T-cell epitopes Biotechnology Genetics Mitea D verfasserin aut Goryunova Svetlana V verfasserin aut van der Meer Ingrid M verfasserin aut Padioleau Ismael verfasserin aut Gilissen Luud JWJ verfasserin aut Koning Frits verfasserin aut Smulders Marinus JM verfasserin aut In BMC Genomics BMC, 2003 13(2012), 1, p 277 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:13 year:2012 number:1, p 277 https://doi.org/10.1186/1471-2164-13-277 kostenfrei https://doaj.org/article/1c7ef484b2b74b9d87dcc960ac63e3cd kostenfrei http://www.biomedcentral.com/1471-2164/13/277 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 13 2012 1, p 277
allfieldsGer	10.1186/1471-2164-13-277 doi (DE-627)DOAJ065167635 (DE-599)DOAJ1c7ef484b2b74b9d87dcc960ac63e3cd DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Salentijn Elma MJ verfasserin aut Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p< Wheat Gluten γ-gliadins Celiac disease T-cell epitopes Biotechnology Genetics Mitea D verfasserin aut Goryunova Svetlana V verfasserin aut van der Meer Ingrid M verfasserin aut Padioleau Ismael verfasserin aut Gilissen Luud JWJ verfasserin aut Koning Frits verfasserin aut Smulders Marinus JM verfasserin aut In BMC Genomics BMC, 2003 13(2012), 1, p 277 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:13 year:2012 number:1, p 277 https://doi.org/10.1186/1471-2164-13-277 kostenfrei https://doaj.org/article/1c7ef484b2b74b9d87dcc960ac63e3cd kostenfrei http://www.biomedcentral.com/1471-2164/13/277 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 13 2012 1, p 277
allfieldsSound	10.1186/1471-2164-13-277 doi (DE-627)DOAJ065167635 (DE-599)DOAJ1c7ef484b2b74b9d87dcc960ac63e3cd DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Salentijn Elma MJ verfasserin aut Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p< Wheat Gluten γ-gliadins Celiac disease T-cell epitopes Biotechnology Genetics Mitea D verfasserin aut Goryunova Svetlana V verfasserin aut van der Meer Ingrid M verfasserin aut Padioleau Ismael verfasserin aut Gilissen Luud JWJ verfasserin aut Koning Frits verfasserin aut Smulders Marinus JM verfasserin aut In BMC Genomics BMC, 2003 13(2012), 1, p 277 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:13 year:2012 number:1, p 277 https://doi.org/10.1186/1471-2164-13-277 kostenfrei https://doaj.org/article/1c7ef484b2b74b9d87dcc960ac63e3cd kostenfrei http://www.biomedcentral.com/1471-2164/13/277 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 13 2012 1, p 277
language	English
source	In BMC Genomics 13(2012), 1, p 277 volume:13 year:2012 number:1, p 277
sourceStr	In BMC Genomics 13(2012), 1, p 277 volume:13 year:2012 number:1, p 277
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Wheat Gluten γ-gliadins Celiac disease T-cell epitopes Biotechnology Genetics
isfreeaccess_bool	true
container_title	BMC Genomics
authorswithroles_txt_mv	Salentijn Elma MJ @@aut@@ Mitea D @@aut@@ Goryunova Svetlana V @@aut@@ van der Meer Ingrid M @@aut@@ Padioleau Ismael @@aut@@ Gilissen Luud JWJ @@aut@@ Koning Frits @@aut@@ Smulders Marinus JM @@aut@@
publishDateDaySort_date	2012-01-01T00:00:00Z
hierarchy_top_id	326644954
id	DOAJ065167635
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">DOAJ065167635</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230502144206.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2012 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/1471-2164-13-277</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ065167635</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ1c7ef484b2b74b9d87dcc960ac63e3cd</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">TP248.13-248.65</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Salentijn Elma MJ</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2012</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"><p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. 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callnumber-first	T - Technology
author	Salentijn Elma MJ
spellingShingle	Salentijn Elma MJ misc TP248.13-248.65 misc QH426-470 misc Wheat misc Gluten misc γ-gliadins misc Celiac disease misc T-cell epitopes misc Biotechnology misc Genetics Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation
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topic_title	TP248.13-248.65 QH426-470 Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation Wheat Gluten γ-gliadins Celiac disease T-cell epitopes
topic	misc TP248.13-248.65 misc QH426-470 misc Wheat misc Gluten misc γ-gliadins misc Celiac disease misc T-cell epitopes misc Biotechnology misc Genetics
topic_unstemmed	misc TP248.13-248.65 misc QH426-470 misc Wheat misc Gluten misc γ-gliadins misc Celiac disease misc T-cell epitopes misc Biotechnology misc Genetics
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title	Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation
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title_full	Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation
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author_browse	Salentijn Elma MJ Mitea D Goryunova Svetlana V van der Meer Ingrid M Padioleau Ismael Gilissen Luud JWJ Koning Frits Smulders Marinus JM
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title_sort	celiac disease t-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation
callnumber	TP248.13-248.65
title_auth	Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation
abstract	<p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p<
abstractGer	<p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p<
abstract_unstemmed	<p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p<
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title_short	Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation
url	https://doi.org/10.1186/1471-2164-13-277 https://doaj.org/article/1c7ef484b2b74b9d87dcc960ac63e3cd http://www.biomedcentral.com/1471-2164/13/277 https://doaj.org/toc/1471-2164
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up_date	2024-07-03T13:22:20.447Z
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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">DOAJ065167635</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230502144206.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2012 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/1471-2164-13-277</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ065167635</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ1c7ef484b2b74b9d87dcc960ac63e3cd</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">TP248.13-248.65</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Salentijn Elma MJ</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2012</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"><p<Abstract</p< <p<Background</p< <p<Celiac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.</p< <p<Results</p< <p<A detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (<it<T. aestivum</it<, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, <it<Gli-A1</it<, <it<Gli-B1</it< or <it<Gli-D1</it<. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus <it<Gli-D1</it<. Transcripts from each locus differed in CD epitope content and composition. The <it<Gli-D1</it< transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the <it<Gli-A1</it< transcripts (8.6) and the <it<Gli-B1</it< transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce <it<in vitro</it< proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.</p< <p<Conclusions</p< <p<Evaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).</p<</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Wheat</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gluten</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">γ-gliadins</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Celiac disease</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">T-cell epitopes</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biotechnology</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mitea D</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" 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Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation

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