Germline-encoded amino acids in the αβ T-cell receptor control thymic selection View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-04

AUTHORS

James P. Scott-Browne, Janice White, John W. Kappler, Laurent Gapin, Philippa Marrack

ABSTRACT

An alphabeta T-cell response depends on the recognition of antigen plus major histocompatibility complex (MHC) proteins by its antigen receptor (TCR). The ability of peripheral alphabeta T cells to recognize MHC is at least partly determined by MHC-dependent thymic selection, by which an immature T cell survives only if its TCR can recognize self MHC. This process may allow MHC-reactive TCRs to be selected from a repertoire with completely random and unbiased specificities. However, analysis of thymocytes before positive selection indicated that TCR proteins might have a predetermined ability to bind MHC. Here we show that specific germline-encoded amino acids in the TCR promote 'generic' MHC recognition and control thymic selection. In mice expressing single, rearranged TCR beta-chains, individual mutation of amino acids in the complementarity-determining region (CDR) 2beta to Ala reduced development of the entire TCR repertoire. Altogether, these results show that thymic selection is controlled by germline-encoded MHC contact points in the alphabeta TCR and indicate that the diversity of the peripheral T-cell repertoire is enhanced by this 'built-in' specificity. More... »

PAGES

1043

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature07812

DOI

http://dx.doi.org/10.1038/nature07812

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017171182

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19262510


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