Exogenous retroviruses were analyzed for their influences on T cell repertoire. A defective murine leukemia virus which causes a mouse acquired immune deficiency syndrome (MAIDS) induced superantigen-like T cell activation in vitro. In vivo, this virus selectively activated and expanded CD4+ T cells expressing Vbeta5, followed later in the course of infection by widespread immune deficiency in all T cells. The effect of milk-borne MMTV on the T cell receptor (TCR) repertoire was analyzed. A previously uncharacterized tumorigenic milk-borne virus in BALB/c mice (the BALB/cV virus) was found to induce deletion of T cells expressing TCR Va2 in developing mice. This effect was MHC-dependent. The roles of MHC class II, TCR, and CD28 costimulatory molecules in susceptibility to MMTV infection was tested. Milk-borne virus induced Vbeta-specific deletion only in strains of mice bearing natural or transgenic I-E class II major histocompatibility complex (MHC) product. Moreover, susceptibility to milk-borne virus as determined by assays of viral pp28 or LTR mRNA was also dependent upon I-E expression. These findings indicate that viral infection is dependent upon superantigenic stimulation of host lymphoid cells. CD28-dependent costimulus was shown to play a role in optimal Vbeta-specific T and B cell responses to in vivo challenge of adult mice with infectious MMTV. In contrast, Vbeta-specific deletion in response to neonatal challenge, as well as susceptibility to infectious milk-borne virus, appeared to be CD28-independent. Although Vbeta-specific superantigenic effects are a useful model for the study of TCR selection, selection may more commonly be on the basis of receptor specificity determined by multiple TCR ` and beta chain components. Analysis of the expression of specific TCR Valpha/Vbeta pairs has indicated that Valpha/Vbeta pairing is non-random and that strain-specific differences exist in patterns of Valpha/Vbeta expression, providing a new approach to the study of repertoire selection. T cell responses to endogenous superantigen were also shown to be influenced by Valpha as well as Vbeta TCR expression.
