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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Meriem Attaf, Stephan J Holland, Istvan Bartok, Julian Dyson

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. More... »

PAGES

35006

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep35006

DOI

http://dx.doi.org/10.1038/srep35006

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031025433

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27775030


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