Toward a predictive understanding of molecular recognition
Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide c...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Weng, Zhiping [verfasserIn] DeLisi, Charles [verfasserIn] |
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| Format: |
E-Artikel |
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| Erschienen: |
Oxford, UK: Blackwell Publishing Ltd ; 1998 |
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| Umfang: |
Online-Ressource |
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| Reproduktion: |
2006 ; Blackwell Publishing Journal Backfiles 1879-2005 |
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| Übergeordnetes Werk: |
In: Immunological reviews - Oxford : Wiley-Blackwell, 1969, 163(1998), 1, Seite 0 |
| Übergeordnetes Werk: |
volume:163 ; year:1998 ; number:1 ; pages:0 |
| Links: |
|---|
| DOI / URN: |
10.1111/j.1600-065X.1998.tb01201.x |
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| 520 | |a Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. | ||
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10.1111/j.1600-065X.1998.tb01201.x doi (DE-627)NLEJ242666825 DE-627 ger DE-627 rakwb Weng, Zhiping verfasserin aut Toward a predictive understanding of molecular recognition Oxford, UK Blackwell Publishing Ltd 1998 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. 2006 Blackwell Publishing Journal Backfiles 1879-2005 |2006|||||||||| DeLisi, Charles verfasserin aut In Immunological reviews Oxford : Wiley-Blackwell, 1969 163(1998), 1, Seite 0 Online-Ressource (DE-627)NLEJ243927398 (DE-600)2038276-5 1600-065X volume:163 year:1998 number:1 pages:0 http://dx.doi.org/10.1111/j.1600-065X.1998.tb01201.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 163 1998 1 0 |
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10.1111/j.1600-065X.1998.tb01201.x doi (DE-627)NLEJ242666825 DE-627 ger DE-627 rakwb Weng, Zhiping verfasserin aut Toward a predictive understanding of molecular recognition Oxford, UK Blackwell Publishing Ltd 1998 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. 2006 Blackwell Publishing Journal Backfiles 1879-2005 |2006|||||||||| DeLisi, Charles verfasserin aut In Immunological reviews Oxford : Wiley-Blackwell, 1969 163(1998), 1, Seite 0 Online-Ressource (DE-627)NLEJ243927398 (DE-600)2038276-5 1600-065X volume:163 year:1998 number:1 pages:0 http://dx.doi.org/10.1111/j.1600-065X.1998.tb01201.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 163 1998 1 0 |
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10.1111/j.1600-065X.1998.tb01201.x doi (DE-627)NLEJ242666825 DE-627 ger DE-627 rakwb Weng, Zhiping verfasserin aut Toward a predictive understanding of molecular recognition Oxford, UK Blackwell Publishing Ltd 1998 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. 2006 Blackwell Publishing Journal Backfiles 1879-2005 |2006|||||||||| DeLisi, Charles verfasserin aut In Immunological reviews Oxford : Wiley-Blackwell, 1969 163(1998), 1, Seite 0 Online-Ressource (DE-627)NLEJ243927398 (DE-600)2038276-5 1600-065X volume:163 year:1998 number:1 pages:0 http://dx.doi.org/10.1111/j.1600-065X.1998.tb01201.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 163 1998 1 0 |
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10.1111/j.1600-065X.1998.tb01201.x doi (DE-627)NLEJ242666825 DE-627 ger DE-627 rakwb Weng, Zhiping verfasserin aut Toward a predictive understanding of molecular recognition Oxford, UK Blackwell Publishing Ltd 1998 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. 2006 Blackwell Publishing Journal Backfiles 1879-2005 |2006|||||||||| DeLisi, Charles verfasserin aut In Immunological reviews Oxford : Wiley-Blackwell, 1969 163(1998), 1, Seite 0 Online-Ressource (DE-627)NLEJ243927398 (DE-600)2038276-5 1600-065X volume:163 year:1998 number:1 pages:0 http://dx.doi.org/10.1111/j.1600-065X.1998.tb01201.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 163 1998 1 0 |
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10.1111/j.1600-065X.1998.tb01201.x doi (DE-627)NLEJ242666825 DE-627 ger DE-627 rakwb Weng, Zhiping verfasserin aut Toward a predictive understanding of molecular recognition Oxford, UK Blackwell Publishing Ltd 1998 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. 2006 Blackwell Publishing Journal Backfiles 1879-2005 |2006|||||||||| DeLisi, Charles verfasserin aut In Immunological reviews Oxford : Wiley-Blackwell, 1969 163(1998), 1, Seite 0 Online-Ressource (DE-627)NLEJ243927398 (DE-600)2038276-5 1600-065X volume:163 year:1998 number:1 pages:0 http://dx.doi.org/10.1111/j.1600-065X.1998.tb01201.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 163 1998 1 0 |
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Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. |
| abstractGer |
Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. |
| abstract_unstemmed |
Summary: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-pep-tide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers.The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions un addressed, including the following; i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other’ iii) What arc the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend?This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths. |
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Toward a predictive understanding of molecular recognition |
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DeLisi, Charles |
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