Expression of a MHC class II transgene determines both superantigenicity and susceptibility to mammary tumor virus infection

Abstract

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 V/3 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 EαEβ class II major histocompatibility complex (MHC) product were exposed to milk borne C3H MMTV. Superantigen-mediated deletion of Vβ14-expressing T cells occurred only in Ea transgene-positive mice, indicating that the deletion was EαEβ 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 EαEβ 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 Eα expression or the Ea-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.