SELECTION OF TCR V-ALPHA BY MHC CLASS-II PREDICTS SUPERANTIGEN REACTIVITY

Recognition of superantigens by T cells predominantly involves the TCR V beta region. The contribution of reactivity from the non-V beta portion of the TCR remains less clear. We have investigated the V-alpha repertoire of T cells bearing one V(b)eta element responding to different superantigen or polyclonal stimuli. The data indicate that the V-alpha chain is not directly involved in superantigen recognition, since unrelated superantigens do not stimulate cells bearing different V-alpha elements. Instead, analysis of V-alpha elements used preferentially in the CD4(+) or CD8(+) cells, shows that the V-alpha-regions predominating in the superantigen response are the same V(alpha)s that are positively selected into the CD4(+) lineage. Thus the ability of a V-alpha-region to either aid or hinder the interaction with class II predicts its frequency in a superantigen-responding population of T cells.