POLYMORPHISM OF THE MHC CLASS-II EB GENE DETERMINES THE PROTECTION AGAINST COLLAGEN-INDUCED ARTHRITIS

被引:41
作者
GONZALEZGAY, MA
ZANELLI, E
KRCO, CJ
NABOZNY, GH
HANSON, J
GRIFFITHS, MM
LUTHRA, HS
DAVID, CS
机构
[1] MAYO CLIN & MAYO GRAD SCH MED,DEPT IMMUNOL,ROCHESTER,MN 55905
[2] MAYO CLIN & MAYO GRAD SCH MED,DEPT RHEUMATOL,ROCHESTER,MN 55905
[3] VET AFFAIRS MED CTR,RES SERV,SALT LAKE CITY,UT 84132
[4] UNIV UTAH,DEPT MED,DIV RHEUMATOL,SALT LAKE CITY,UT 84132
关键词
D O I
10.1007/BF00164985
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (De homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E beta(d) molecule prevents CIA development in susceptible H2(q) mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F-1 mice, only H2Eb(d) and H2Eb(s) molecules showed protection. Using recombinant B10.RDD (Eb(d/b)) mice, we found that CIA protection was mediated by the first domain of the E beta(d) molecule. Using peptides covering the third hypervariable region of the E beta chain, we found a perfect correlation between presentation of E beta peptides by the H2A(q) molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2A(q) molecule.
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页码:35 / 40
页数:6
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