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

W A Simmons, L Y Leong, N Satumtira, G W Butcher, J C Howard, J A Richardson, C A Slaughter, R E Hammer and J D Taurog
J Immunol February 15, 1996, 156 (4) 1661-1667;
W A Simmons
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L Y Leong
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N Satumtira
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G W Butcher
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J C Howard
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J A Richardson
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C A Slaughter
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R E Hammer
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J D Taurog
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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 cimb/b targets significantly less well than cima/a or cima/b targets. Addition of exogenous H-Y peptides to male B27 cimb/b targets increased susceptibility to lysis to the level of cima/a targets. Male B27 cimb/b cells were less efficient than cima/a cells in competitively inhibiting CTL lysis of female B27 cima/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 backcross rats bearing either cima/b or cimb/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.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 156, Issue 4
15 Feb 1996
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Rat MHC-linked peptide transporter alleles strongly influence peptide binding by HLA-B27 but not B27-associated inflammatory disease.
W A Simmons, L Y Leong, N Satumtira, G W Butcher, J C Howard, J A Richardson, C A Slaughter, R E Hammer, J D Taurog
The Journal of Immunology February 15, 1996, 156 (4) 1661-1667;

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Rat MHC-linked peptide transporter alleles strongly influence peptide binding by HLA-B27 but not B27-associated inflammatory disease.
W A Simmons, L Y Leong, N Satumtira, G W Butcher, J C Howard, J A Richardson, C A Slaughter, R E Hammer, J D Taurog
The Journal of Immunology February 15, 1996, 156 (4) 1661-1667;
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Print ISSN 0022-1767        Online ISSN 1550-6606