Gonzalez-Gay M A, Zanelli E, Krco C J, Nabozny G H, Hanson J, Griffiths M M, Luthra H S, David C S
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Immunogenetics. 1995;42(1):35-40. doi: 10.1007/BF00164985.
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 (DQ 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 H2q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F1 mice, only H2Ebd and H2Ebs molecules showed protection. Using recombinant B10.RDD (Ebd/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 H2Aq 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 H2Aq molecule.
胶原诱导性关节炎（CIA）是一种自身免疫性多关节炎的动物模型，与类风湿关节炎（RA）有相似之处。矛盾的是，小鼠对CIA的易感性由H2A基因座（DQ同源）控制，而RA与HLA - DR基因（H2E同源）相关。我们最近发现，Eβd分子可阻止易感H2q小鼠发生CIA。我们探讨了H2Eb多态性是否会像HLA - DRB1多态性在RA中那样影响CIA发病率的问题。在F1小鼠中，只有H2Ebd和H2Ebs分子表现出保护作用。使用重组B10.RDD（Ebd/b）小鼠，我们发现CIA保护作用是由Eβd分子的第一个结构域介导的。使用覆盖Eβ链第三个高变区的肽段，我们发现H2Aq分子呈递Eβ肽段与对CIA的保护作用之间存在完美的相关性。因此，H2Eb预防CIA的机制似乎依赖于Eβ肽段与H2Aq分子的亲和力。
