EXPRESSION OF MTV-7 SAG GENE IN-VIVO USING A RETROVIRAL VECTOR RESULTS IN SELECTIVE INACTIVATION OF SUPERANTIGEN REACTIVE T-CELLS

T cells expressing specific TCR Vbeta chains are intrathymically elimi nated in mice expressing the murine Mls (minor lymphocyte stimulating) superantigens. Recently, in vitro studies have shown that the endogen ous mouse mammary tumor virus (MMTV)-7 sag gene encodes Mls-1 Ag. The demonstrated ability of MMTV superantigen proteins to react with TCRs has led to the postulate that other infectious retroviruses may use su perantigen-like molecules to modify the host's immune system. In this report, successful retrovirus-mediated Mtv-7 sag gene transfer into pl uripotent hematopoietic stem cells is described. In two different stra ins of Mls-1- host mice (CBA/Ca and BALB/c) reconstituted with Mtv-7 s ag gene expressing bone marrow cells, low levels of ectopic Mtv-7 sag gene expression on syngeneic donor hematopoietic stem cell-derived pop ulation alone can induce partial clonal deletion of Mls-1 reactive Vbe ta6+ and Vbeta8.1+ T cells, and complete clonal inactivation of Vbeta8 .1+ T cells.