αβ T cell receptor germline CDR regions moderate contact with MHC ligands and regulate peptide cross-reactivity

Attaf, Meriem, Holland, Stephan J., Bartok, Istvan and Dyson, Julian 2016. αβ T cell receptor germline CDR regions moderate contact with MHC ligands and regulate peptide cross-reactivity. Scientific Reports 6 (1) , 35006. 10.1038/srep35006

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Abstract

αβ T cells respond to peptide epitopes presented by major histocompatibility complex (MHC) molecules. The role of T cell receptor (TCR) germline complementarity determining regions (CDR1 and 2) in MHC restriction is not well understood. Here, we examine T cell development, MHC restriction and antigen recognition where germline CDR loop structure has been modified by multiple glycine/alanine substitutions. Surprisingly, loss of germline structure increases TCR engagement with MHC ligands leading to excessive loss of immature thymocytes. MHC restriction is, however, strictly maintained. The peripheral T cell repertoire is affected similarly, exhibiting elevated cross-reactivity to foreign peptides. Our findings are consistent with germline TCR structure optimising T cell cross-reactivity and immunity by moderating engagement with MHC ligands. This strategy may operate alongside co-receptor imposed MHC restriction, freeing germline TCR structure to adopt this novel role in the TCR-MHC interface.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	This work is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Nature Publishing Group
ISSN:	2045-2322
Date of First Compliant Deposit:	5 July 2017
Date of Acceptance:	22 September 2016
Last Modified:	05 May 2023 16:49
URI:	https://orca.cardiff.ac.uk/id/eprint/102079

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