Genetic analysis of the effects of Mtv-2 on the T cell repertoire in the WXG-2 mouse strain

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Abstract
In this report, the T cell repertoire was studied In a natural genetic model system using a novel mouse strain (WXG-2) carrying a single pathogenic mouse mammary tumor virus (MMTV) provirus (Mtv-2) on an otherwise MMTV-free genetic background. The Mtv-2 provirus has complete biological activity, produces infectious mllk-transmltted virus, and contributes to mammary carclnogenesis by an insertion mutation mechanism. In mice carrying the Mtv-2 provirus, T cells expressing Vβ14 were specifically deleted in mice with a functional MHC class II I-E gene but not in I-E− controls. The deletion of Vβ14+ T cells was more rapid in mice with the Mtv-2 provirus than in Mtv-2-free control mice infected with exogenous MMTV. In addition, the Mtv-2 deletion phenotype was age dependent. A slow depletion of Vβ14+ T cells was observed, and >95% of the Vβ14+ T cells were eliminated by 6 months of age. These experiments Indicate that (i) the Mtv-2 provirus encodes or regulates expression of a Vβ14-specific superantigen, (ii) interactions between Mtv-2 and other MMTV proviruses are not necessary for the Vβ14 deletion phenotype, (ill) the presence of a retroviral superantigen in all cells is not sufficient for T cell depletion during neonatal development in the thymus, and (iv) the Mtv-2 provirus and Its associated exogenous provirus have the same Vβ specificity. The biological implications of this viral function are presently unknown; however, it is clear that MMTV can have profound effects on the immune system and these effects may ultimately prove to be involved in viral pathogenesis.

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