EXPRESSION OF 2 STRUCTURALLY IDENTICAL VIRAL SUPERANTIGENS RESULTS INTHYMIC ELIMINATION AT DISTINCT DEVELOPMENTAL STAGES

Mouse mammary tumor virus proviral integrants encode superantigens. De veloping thymocytes bearing TCRs with particular V beta elements encou nter these endogenous viral superantigens as self molecules in the thy mus and are consequently clonally eliminated. To study this mechanism of tolerance induction, we have bred B10.BR-Mtv-1 and B10.BR-Mtv-6 mic e, which carry either Mtv-1 or Mtv-6 proviruses but are otherwise gene tically identical. The protein products of these mouse mammary tumor v irus integrants, vSAG1 and vSAG6, both interact with V beta 3(+) T cel ls and have identical amino acid sequences. Interestingly, vSAG6 expre ssion results in the complete deletion of V beta 3(+) peripheral T cel ls, whereas vSAG1 expression results in only partial deletion. Flow cy tometric analyses indicate that B10.BR-Mtv-6 mice delete V beta 3(+) t hymocytes at the immature CD4(+)8(+) stage, whereas B10.BR-Mtv-1 mice delete only mature CD4(+) or CD8(+) cells. In addition, the two strain s exhibit different time courses of thymic deletion: neonatal B10.BR-M tv-6 mice eliminate V beta 3(+) T cells by day 2, in contrast to B10.B R-Mtv-1 mice in which deletion does not occur until day 15. RNase prot ection assays demonstrate that B10.BR-Mtv-6 mice have significantly gr eater thymic vSAG6 mRNA expression levels than vSAG1 levels in B10.BR- Mtv-1 animals, correlating with a more complete deletion of reactive t hymocytes at an earlier point in the maturational sequence.