SUPERANTIGEN IMPLICATED IN DEPENDENCE OF HIV-1 REPLICATION IN T-CELLS ON TCR V-BETA EXPRESSION

IN the pathogenesis of AIDS it is not yet understood whether the small fraction of CD4+ T cells (approximately 1%) infected with the human immunodeficiency virus (HIV) are randomly targeted or not. Here we present evidence that human CD4 T-cell lines expressing selected T-cell antigen receptor V-beta gene products can all be infected in vitro with HIV-1, but give markedly different titres of HIV-1 virion production. For example, V-beta-12 T-cell lines from several unrelated donors reproducibly yielded up to 100-fold more gag gene product (p24gag antigen) than V-beta-6.7a lines. This is consistent with a superantigen effect, because the V-beta selectivity was observed with several divergent HIV-1 isolates, was dependent on antigen-presenting cells and on major histocompatibility complex (MHC) class II but was not MHC class II-restricted. The in vivo significance of these findings is supported by the preferential stimulation of V-beta-12+ T cells by freshly obtained irradiated antigen-presenting cells from some HIV-1-seropositive but not HIV-1-negative donors. Moreover, cells from patients positive for viral antigen (gp120) were enriched in the V-beta-12 subpopulation. V-beta-12+ T cells were not deleted in AIDS patients, however, raising the possibility that a variety of mechanisms contribute to T-cell depletion. Our results indicate that a superantigen targets a subpopulation of CD4+ cells for viral replication.