MHC CLASS-II HIERARCHY OF SUPERANTIGEN PRESENTATION PREDICTS EFFICIENCY OF INFECTION WITH MOUSE MAMMARY-TUMOR VIRUS

Superantigens (SAgs) encoded by infectious mouse mammary tumor viruses (MMTVs) play a crucial role in the viral life cycle. Their expression by infected a cells induces a proliferative immune response by SAg-re active T cells which amplifies MMTV infection. This response most like ly ensures stable MMTV infection and transmission to the mammary gland . Since T cell reactivity to SAgs from endogenous Mtv loci depends on MHC class II molecules expressed by B cells, we have determined the ab ility of MMTV to infect various MHC congenic mice. We show that MHC cl ass II I-E(+) compared with I-E(-) mouse strains show higher levels of MMTV infection, most likely due to their ability to induce a vigorous SAg-dependent immune response following MMTV encounter. Inefficient i nfection is observed in MHC class II I-E(-) mice, which have been show n to present endogenous SAgs poorly. Therefore, during MMTV infection the differential ability of MHC class II molecules to form a functiona l complex with SAg determines the magnitude of the proliferative respo nse of SAg-reactive T cells. This in turn influences the degree of T c ell help provided to infected a cells and therefore the efficiency of amplification of MMTV infection.