HUMAN T-CELLS RESPOND TO MOUSE MAMMARY-TUMOR VIRUS-ENCODED SUPERANTIGEN - V-BETA RESTRICTION AND CONSERVED EVOLUTIONARY FEATURES

Mouse mammary tumor virus (MMTV)-encoded superantigens (SAGs) influenc e the murine T cell repertoire and stimulate a strong mixed lymphocyte response in vitro. These SAGs are encoded by the open reading frame o f the 3' long terminal repeat of MMTV, termed MMTV SAGs. The T cell re sponse to MMTV SAGs is Vbeta restricted and requires expression of the class II molecules of the major histocompatibility complex (MHC) on t he presenting cells. While human T cells respond to bacterial SAGs, it is not known if human T cells or human MHC class II molecules can int eract with MMTV SAGs. A fibroblastic cell line expressing the human MH C class II molecule HLA-DR1 and the Mtv-7 sag gene encoding Mls-1 was used to stimulate human T cells. We show here that human T cells effic iently proliferate in response to Mls-1 presented by HLA-DR1. This T c ell response was inhibited by mAbs directed against CD4 or MHC class I I molecules but not by mAbs specific for CD8 or MHC class I molecules. Moreover, the response to Mls-1 was limited to human T cells expressi ng a restricted set of T cell receptor Vbeta chains. Human T cells exp ressing Vbeta12, 13, 14, 15, and 23 were selectively amplified after M tv-7 sag stimulation. Interestingly, these human Vbetas share the high est degree of homology with the mouse Vbetas interacting with Mls-1. T hese results show a strong evolutionary conservation of the structures required for the presentation and the response to retrovirally encode d endogenous SAGs, raising the possibility that similar elements opera te in humans to shape the T cell repertoire.