T cell receptor V alpha 4 is expressed by a subpopulation of V beta 6 T cells that respond to the bacterial superantigen staphylococcal enterotoxin B.

A subpopulation of murine minor lymphocyte-stimulating locus Ag (Mls)-1a-responsive, TCR V beta 6-expressing T hybrids was responsive to the superantigenic bacterial toxin, staphylococcal enterotoxin B (SEB), presented by murine MHC class II molecules. Comparative functional and surface marker analyses showed that this heterogeneity was not caused by nonspecific effects. It seemed, therefore, that the ability of the TCR V beta 6 T hybrids to respond to SEB was regulated by non-V beta TCR elements. cDNA sequencing analyses of the TCR beta- and alpha-chains expressed by the V beta 6 T hybrids and a beta-chain cDNA gene transfer experiment indicated that although J beta, CDR3 beta, J alpha, and CDR3 alpha were not the relevant elements, SEB responsiveness did correlate with the expression of two different members of the V alpha 4 family. A functional analysis of a separate panel of V alpha 4 T hybrids expressing different V beta elements, including V beta 6, specifically associated SEB responsiveness with the V alpha 4, V beta 6 combination. Overall, the data obtained with both panels of T hybrids showed SEB responsiveness in five out of five V beta 6, V alpha 4 T hybrids, and not in either 11 V beta 6 T hybrids expressing a variety of other V alpha elements or four V alpha 4 T hybrids expressing V beta 11, 14, and 15 elements. Thus, our experiments show for the first time a specific, positive qualitative effect of a defined V alpha element on responsiveness to a bacterial superantigen. Finally, this study has identified four new V alpha elements.