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 tha t induces mammary carcinoma. Infectious MMTV, as well as genomically i ntegrated mouse mammary proviruses, encode superantigens that are reco gnized by T cells that express appropriate T cell receptor Vbeta produ cts. To determine the relationship between the superantigenic property of milk-borne MMTV and its in vivo infectivity, mice which were eithe r positive or negative for expression of a transgene-encoded EalphaEbe ta class II major histocompatibility complex (MHC) product were expose d to milk borne C3H MMTV. Superantigen-mediated deletion of Vbeta14-ex pressing T cells occurred only in Ealpha transgene-positive mice, indi cating that the deletion was EalphaEbeta dependent. When mice were ana lyzed for viral infection by assaying viral p28 in the milk of recipie nt females, significant p28 levels were found only in EalphaEbeta tran sgene-positive mice. Similarly, the presence of C3H MMTV LTR mRNA in m ammary glands, as detected by PCR, paralleled p28 levels. These findin gs indicate that Ealpha expression or the Ealpha-dependent T cell resp onse to viral superantigen is causally related to susceptibility to MM TV infection, and that lack of a permissive class II product can prote ct mice from virus infection.