[PDF][PDF] Dependence of T cell antigen recognition on T cell receptor-peptide MHC confinement time

M Aleksic, O Dushek, H Zhang, E Shenderov, JL Chen… - Immunity, 2010 - cell.com
M Aleksic, O Dushek, H Zhang, E Shenderov, JL Chen, V Cerundolo, D Coombs
Immunity, 2010cell.com
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) …
Summary
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 (kon) and off rate (koff) 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 kon in T cell activation and reconciles apparently contradictory reports on the role of TCR-pMHC binding kinetics and affinity in T cell activation.
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