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 Repjournal_title
Scientific reportsauthors
Zhang H,Lim HS,Knapp B,Deane CM,Aleksic M,Dushek O,van der Merwe PAdoi
10.1038/srep35326subject
Has Abstractpub_date
2016-10-13 00:00:00pages
35326issn
2045-2322pii
srep35326journal_volume
6pub_type
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