Expression of two structurally identical viral superantigens results in thymic elimination at distinct developmental stages
Morishima, C.; Norby-Slycord, C.; McConnell, K.R.; Finch, R.J.; Nelson, A.J.; Farr, A.G.; Pullen, A.M.
Journal of Immunology 153(11): 5091-5103
ISSN/ISBN: 0022-1767 PMID: 7963568 Accession: 008665345
Mouse mammary tumor virus proviral integrants encode superantigens. Developing thymocytes bearing TCRs with particular V-beta elements encounter these endogenous viral superantigens as self molecules in the thymus and are consequently clonally eliminated. To study this mechanism of tolerance induction, we have bred B10.BR-Mtv-1 and B10.BR-Mtv-6 mice, which carry either Mtv-1 or Mtv-6 proviruses but are otherwise genetically identical. The protein products of these mouse mammary tumor virus integrants, vSAG1 and vSAG6, both interact with V-beta-3+ T cells and have identical amino acid sequences. Interestingly, vSAG6 expression results in the complete deletion of V-beta-3+ peripheral T cells, whereas vSAG1 expression results in only partial deletion. Flow cytometric analyses indicate that B10.BR-Mtv-6 mice delete V-beta-3+ thymocytes at the immature CD4+8+ stage, whereas B10.BR-Mtv-1 mice delete only mature CD4+ or CD8+ cells. In addition, the two strains exhibit different time courses of thymic deletion: neonatal B10.BR-Mtv-6 mice eliminate V-beta-3+ T cells by day 2, in contrast to B10.BR-Mtv-1 mice in which deletion does not occur until day 15. RNase protection assays demonstrate that B10.BR-Mtv-6 mice have significantly greater thymic vSAG6 mRNA expression levels than vSAG1 levels in B10.BR-Mtv-1 animals, correlating with a more complete deletion of reactive thymocytes at an earlier point in the maturational sequence.