Germline-encoded amino acids in the alphabeta T-cell receptor control thymic selection.
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.
Scott-Browne
James P
JP
Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA. james.scott-browne@ucdenver.edu
White
Janice
J
Kappler
John W
JW
Gapin
Laurent
L
Marrack
Philippa
P
D000596:Amino Acids / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002678:Chimera / Q000276:immunology / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005854:Germ Cells / Q000378:metabolism*; D006825:Hybridomas / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*
D000596:Amino Acids; D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta