EXPRESSION OF A MHC CLASS-II TRANSGENE DETERMINES BOTH SUPERANTIGENICITY AND SUSCEPTIBILITY TO MAMMARY-TUMOR VIRUS-INFECTION

Milk-borne mouse mammary tumor virus (MMTV) is a type B retrovirus that induces mammary carcinoma. Infectious MMTV, as well as genomically integrated mouse mammary proviruses, encode superantigens that are recognized by T cells that express appropriate T cell receptor Vbeta products. To determine the relationship between the superantigenic property of milk-borne MMTV and its in vivo infectivity, mice which were either positive or negative for expression of a transgene-encoded EalphaEbeta class II major histocompatibility complex (MHC) product were exposed to milk borne C3H MMTV. Superantigen-mediated deletion of Vbeta14-expressing T cells occurred only in Ealpha transgene-positive mice, indicating that the deletion was EalphaEbeta dependent. When mice were analyzed for viral infection by assaying viral p28 in the milk of recipient females, significant p28 levels were found only in EalphaEbeta transgene-positive mice. Similarly, the presence of C3H MMTV LTR mRNA in mammary glands, as detected by PCR, paralleled p28 levels. These findings indicate that Ealpha expression or the Ealpha-dependent T cell response to viral superantigen is causally related to susceptibility to MMTV infection, and that lack of a permissive class II product can protect mice from virus infection.