Control of MHC restriction by TCR V-alpha CDR1 and CDR2

Individual T cell receptor (TCR) V-alpha elements are expressed preferentially in CD4 or CD8 peripheral T cell subsets. The closely related V(alpha)3.1 and V(alpha)3.2 elements show reciprocal selection into CD4 and CD8 subsets, respectively. Transgenic mice expressing site-directed mutants of a V alpha 3.1 gene were used to show that individual residues in either the complementarity-determining region 1 (CDR1) or CDR2 were sufficient to change selection from the CD4 subset to the CD8 subset. Thus, the germline-encoded V-alpha elements are a major influence on major histocompatibility class complex (MHC) restriction, most likely by a preferential interaction with one or the other class of MHC molecule.