Rat MHC-linked peptide transporter alleles strongly influence peptide binding by HLA-B27 but not B27-associated inflammatory disease

William A. Simmons, Louise Y.W. Leong, Nimman Satumtira, Geoffrey W. Butcher, Jonathan C. Howard, James A. Richardson, Clive A. Slaughter, Robert E. Hammer, Joel D. Taurog

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Rats transgenic for the human MHC molecule HLA-B27 were used to study the effect of two alleles, cima and cimb, which are associated with peptide transport by the MHC-encoded Tap2 transporter, on the function of HLA-B27 as a restriction element for CTL recognition of the male H-Y minor H Ag and on the multisystem inflammatory disease characteristic of B27 transgenic rats. Anti-H-Y CTL generated in cima B27 transgenic rats lysed male B27 cim(b/b) targets significantly less well than cim(a/a) or cim(a/b) targets. Addition of exogenous H-Y peptides to male B27 cim(b/b) targets increased susceptibility to lysis to the level of cim(a/a) targets. Male B27 cim(b/b) cells were less efficient than cim(a/a) cells in competitively inhibiting CTL lysis of female B27 cim(a/a) targets sensitized with exogenous H-Y peptides. 3H-Labeled peptides eluted from B27 molecules of lymphoblasts from rats of two cimb and three cima RT1 haplotypes showed that the cimb peptide pool favors comparatively longer and/or more hydrophobic peptides. These results indicate that RT1-linked Tap2 polymorphism in the rat strongly influences peptide loading of HLA-B27. Nonetheless, the prevalence and severity of multisystem inflammatory lesions were comparable in back-cross rats bearing either cim(a/b) or cim(b/b). It thus appears either that binding of specific peptides to B27 is unimportant in the pathogenesis of B27-associated disease or that the critical peptides, unlike H-Y and many others, are not influenced by Tap transporter polymorphism.

Original languageEnglish (US)
Pages (from-to)1661-1667
Number of pages7
JournalJournal of Immunology
Volume156
Issue number4
StatePublished - Feb 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Simmons, W. A., Leong, L. Y. W., Satumtira, N., Butcher, G. W., Howard, J. C., Richardson, J. A., Slaughter, C. A., Hammer, R. E., & Taurog, J. D. (1996). Rat MHC-linked peptide transporter alleles strongly influence peptide binding by HLA-B27 but not B27-associated inflammatory disease. Journal of Immunology, 156(4), 1661-1667.