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- Title
Germline-encoded amino acids in the αβ T-cell receptor control thymic selection.
- Authors
Scott-Browne, James P.; White, Janice; Kappler, John W.; Gapin, Laurent; Marrack, Philippa
- Abstract
An αβ T-cell response depends on the recognition of antigen plus major histocompatibility complex (MHC) proteins by its antigen receptor (TCR). The ability of peripheral αβ 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 β-chains, individual mutation of amino acids in the complementarity-determining region (CDR) 2β 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 αβ TCR and indicate that the diversity of the peripheral T-cell repertoire is enhanced by this ‘built-in’ specificity.
- Subjects
LETTERS to the editor; AMINO acids
- Publication
Nature, 2009, Vol 458, Issue 7241, p1043
- ISSN
0028-0836
- Publication type
Letter
- DOI
10.1038/nature07812