The contribution of major histocompatibility complex contacts to the affinity and kinetics of T cell receptor binding.

Abstract:

:The interaction between the T cell antigen receptor (TCR) and antigenic peptide in complex with major histocompatibility complex (MHC) molecules is a crucial step in T cell activation. The relative contributions of TCR:peptide and TCR:MHC contacts to the overall binding energy remain unclear. This has important implications for our understanding of T cell development and function. In this study we used site directed mutagenesis to estimate the contribution of HLA-A2 side-chains to the binding of four TCRs. Our results show that these TCRs have very different energetic 'footprints' on HLA-A2, with no residues contributing to all TCR interactions. The estimated overall contribution of MHC side-chains to the total interaction energy was variable, with lower limits ranging from 11% to 50%. Kinetic analysis suggested a minor and variable contribution of MHC side-chains to the transition state complex, arguing against a two-step mechanism for TCR binding.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Zhang H,Lim HS,Knapp B,Deane CM,Aleksic M,Dushek O,van der Merwe PA

doi

10.1038/srep35326

subject

Has Abstract

pub_date

2016-10-13 00:00:00

pages

35326

issn

2045-2322

pii

srep35326

journal_volume

6

pub_type

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