CONTROL OF MHC RESTRICTION BY TCR V-ALPHA CDR1 AND CDR2

Individual T cell receptor (TCR) V-alpha elements are expressed prefer entially 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 CD 4 and CD8 subsets, respectively. Transgenic mice expressing site-direc ted mutants of a V alpha 3.1 gene were used to show that individual re sidues in either the complementarity-determining region 1 (CDR1) or CD R2 were sufficient to change selection from the CD4 subset to the CD8 subset. Thus, the germline-encoded V-alpha elements are a major influe nce on major histocompatibility class complex (MHC) restriction, most likely by a preferential interaction with one or the other class of MH C molecule.