Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V β expression

Abstract

IN the pathogenesis of AIDS it is not yet understood whether the small fraction of CD4⁺ T cells (~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 Vβ gene products can all be infected in vitro with HIV-1, but give markedly different titres of HIV-1 virion production. For example, Vβ12 T-cell lines from several unrelated donors reproducibly yielded up to 100-fold more gag gene product (p24^gag antigen) than Vβ6.7a lines. This is consistent with a superantigen effect, because the Vβ 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 Vβ12⁺ 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 Vβ12 subpopulation. Vβ12⁺ 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.