The use of mammary tumor virus (Mtv)-negative and single-Mtv mice to evaluate the effects of endogenous viral superantigens on the T cell repertoire

Most laboratory strains of mice have between two and eight endogenous superantigens. These viral superantigens (vSAGs) are coded by genes in the 3' long terminal repeats of endogenous mammary tumor viruses (Mtv's). A line of Mtv-negative mice and several lines of mice containing single Mtv's were created by inbreeding the F₂ progeny of CBA/CaJ and C58/J mice, which have no Mtv integrants in common. This allowed the T cell repertoire of H-2(k) mice, unaffected by Mtv superantigens, as well as the effects of vSAGs upon that repertoire, to be studied. Although each individual mouse had a different mix of C58/J and CBA/CaJ background genes, the T cell repertoires of different Mtv-negative mice were very similar and were reproducible. Since the background genes did not affect the Vβ repertoire, there are no superantigens, other than those encoded by Mtv's, that differ between CBA/CaJ and C58/J. CD4 and CD8 T cells had quite different repertoires in the Mtv- negative mice because of the effects of class I and class II major histocompatibility complex molecules on positive and negative selection. vSAG3 was found to delete Vβ5 T cells, while vSAG8 deleted Vβ7 T cells, and vSAG9 deleted Vβ13 T cells in addition to their previously reported specificities. vSAG17 deletes a small proportion of CD4⁺ T cells bearing Vβ11 and -12. vSAG14 and -30 have little effect on the T cell repertoire and are not expressed in thymocytes and splenocytes. An endogenous superantigen that has a low avidity for a particular Vβ may positively select thymocytes, leading to an increased frequency off peripheral T cells bearing the relevant Vβs. We found evidence that vSAG11 may positively select T cells bearing Vβ8.2. Our data, which analyzed the effects of seven endogenous Mtv's, showed little evidence of positive selection by any other vSAGs on T cells bearing any Vβ tested, despite published reports to the contrary.