| First Author | Scott-Browne JP | Year | 2009 |
| Journal | Nature | Volume | 458 |
| Issue | 7241 | Pages | 1043-6 |
| PubMed ID | 19262510 | Mgi Jnum | J:148005 |
| Mgi Id | MGI:3843141 | Doi | 10.1038/nature07812 |
| Citation | Scott-Browne JP, et al. (2009) Germline-encoded amino acids in the alphabeta T-cell receptor control thymic selection. Nature 458(7241):1043-6 |
| abstractText | 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. |
