When T cell receptor (TCR) expression was analyzed by flow cytometry and by mRNA quantitation, strain-specific decreases were detected in expression of 12 of the 22 known mouse Vbeta products, representing negative selection of potentially self-reactive T cells in mice expressing the corresponding self ligands. These deleting ligands also functioned as """"""""superantigens"""""""" capable of stimulating T cells expressing the corresponding Vbeta products. Genetic mapping in all cases identified endogenous mouse mammary tumor (MMTV) proviruses encoding the Vbeta-specific deleting ligands. These Vbeta deletions fail to occur in athymic nude mice, demonstrating that the thymus is critical in tolerance by negative selection. Exogenous viruses were analyzed for their influences on T cell repertoire. Milk-borne MMTV induced Vbeta-14 deletion only in strains of mice bearing natural or transgenic I-E class II major histocompatibility complex (MHC) product. A 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 Vbeta-5, followed later in the course of infection by widespread immune deficiency in all T cells. Although Vbeta-specific superantigen effects are a model for the study of TCR selection, selection may more commonly depend on receptor specificity determined by multiple TCR alpha 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. When TCR expression was analyzed in xenogeneic bone marrow transplantation between mouse and rat, it was found that tolerance to xenograft was accompanied by Vbeta-specific T cell deletions. In the class I-restricted response of mouse CD8+ T cells to HIV peptides, unique cross-reactive specificity patterns were accompanied by highly preferential use of specific Vbeta products.
