Dependence of T cell antigen recognition on T cell receptor-peptide MHC confinement time.
Immunity
; 32(2): 163-74, 2010 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-20137987
ABSTRACT
T cell receptor (TCR) binding to diverse peptide-major histocompatibility complex (pMHC) ligands results in various degrees of T cell activation. Here we analyze which binding properties of the TCR-pMHC interaction are responsible for this variation in pMHC activation potency. We have analyzed activation of the 1G4 cytotoxic T lymphocyte clone by cognate pMHC variants and performed thorough correlation analysis of T cell activation with 1G4 TCR-pMHC binding properties measured in solution. We found that both the on rate (k(on)) and off rate (k(off)) contribute to activation potency. Based on our results, we propose a model in which rapid TCR rebinding to the same pMHC after chemical dissociation increases the effective half-life or "confinement time" of a TCR-pMHC interaction. This confinement time model clarifies the role of k(on) in T cell activation and reconciles apparently contradictory reports on the role of TCR-pMHC binding kinetics and affinity in T cell activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Receptores de Antígenos de Linfócitos T
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Linfócitos T Citotóxicos
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Antígeno HLA-A2
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Proteínas de Neoplasias
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido