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.

Abstract

SummaryMost 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 V[3 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-negafive 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 V[35 T cells, while vSAG8 deleted V[37 T cells, and vSAG9 deleted V[313 T cells in addition to their previously reported specificities, vSAG17 deletes a small proportion ofCD4 + T cells bearing V[311 and -12. vSAG14 and -30 have httle 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 V[3 may positively select thymocytes, leading to an increased frequency of peripheral T cells bearing the relevant V[3s. We found evidence that vSAG11 may positively select T cells bearing V[38.2. 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 V[3 tested, despite published reports to the contrary.

Requirement for a Complex Array of Costimulators in the Negative Selection of Autoreactive Thymocytes In Vivo

“…3, top). This result would be expected if V␤11 ϩ T cells are being rescued from Mtv-8,9-induced deletion, because it is well documented that the V␤8.1/8.2 population behaves in a compensatory fashion in the presence of these SAg (43)(44)(45)(46). Similar results were observed in the V␤8.1/8.2 profile of the splenocytes as well (data not shown).…”

“…However, this is unlikely because in the cases where we screened for Mtv-6 expression, we did not observe a significant effect of Mtv-6 on V␤5 deletion over and above that already due to Mtv-8,9 (data not shown). Correspondingly, single Mtv mice reveal that Mtv-9 alone can delete 80 -98% of the V␤5 ϩ CD4 ϩ T cells (43). A more likely possibility is that deletion of V␤5 ϩ or V␤11 ϩ thymocytes occurs at different stages of thymocyte development or is regulated by different APC.…”

“…Mtv-6 deletes V␤3-and V␤5-bearing T cells, and Mtv-8,9 delete V␤5-, V␤11-, and V␤12-bearing T cells (43). Since Mtv-30 is probably not expressed, and since Mtv-17 has very little effect on V␤11 deletion in comparison to Mtv-8,9 (43), we did not screen for Mtv-17,30.…”

“…Therefore, we examined V␤8.1/8.2 profiles, since these T cells are not deleted by Mtv-6, -8, or -9 (43), and this population is therefore commonly used as a control for Mtv-6,8,9-specific deletion (44 -46). The percentage of V␤8.1/8.2 ϩ cells did not increase in the costimulator-null mice (Fig.…”

Receptor revision in CD4 T cells is influenced by follicular helper T cell formation and germinal-center interactions

“…Vβ5 + TCRs interact with an extrathymic superantigen (superAg) encoded by mouse mammary tumor virus 8 (Mtv-8), a defective retrovirus (17,18). Mtv-8 is very poorly expressed and only weakly stimulates T cells (17)(18)(19).…”