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.
journal_name
Naturejournal_title
Natureauthors
Scott-Browne JP,White J,Kappler JW,Gapin L,Marrack Pdoi
10.1038/nature07812subject
Has Abstractpub_date
2009-04-23 00:00:00pages
1043-6issue
7241eissn
0028-0836issn
1476-4687pii
nature07812journal_volume
458pub_type
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