Expression of two structurally identical viral superantigens results in thymic elimination at distinct developmental stages.
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.
Department of Immunology, University of Washington, Seattle 98195.
C
C
Morishima
C
C
Norby-Slycord
K R
KR
McConnell
R J
RJ
Finch
A J
AJ
Nelson
A G
AG
Farr
A M
AM
Pullen
D000818:Animals; D001483:Base Sequence; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013154:Spleen / Q000166:cytology; D018089:Superantigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens