大鼠胶原诱导性关节炎的免疫遗传学。主要组织相容性复合体（MHC）和非MHC基因产物均决定了对牛和鸡Ⅱ型胶原免疫反应的表位特异性。

Immunogenetics of collagen-induced arthritis in rats. Both MHC and non-MHC gene products determine the epitope specificity of immune response to bovine and chick type II collagens.

作者信息

Griffiths M M, Cremer M A, Harper D S, McCall S, Cannon G W

机构信息

Research Service, Veterans Administration Medical Center, Salt Lake City, Utah.

出版信息

J Immunol. 1992 Jul 1;149(1):309-16.

PMID:1376750

Abstract

Seven inbred, RT1-congenic rat strains were immunized with native bovine (BII), porcine (PII), or chick (CII) type II collagen and observed for onset, incidence, and severity of arthritis. Clinical results were compared with IgG reactive with native rat type II collagen (RII) and the purified, renatured cyanogen-bromide peptides of BII, CII, or RII. Immunodominant responses to CB11, CB9,7, and CB12 of RII were identified. Secondary responses to CB8 and CB10 also occurred. Reproducible patterns of peptide reactivity were defined in each strain and reflected both RT1 and non-RT1 genotypes plus the species of immunizing collagen. BN non-RT1 gene products moderated clinical arthritis but increased the levels of reactivity to CB11 in three strains carrying RT1l,n,av1 haplotypes. WF (RT1u) rats were susceptible to collagen-induced arthritis (CIA) and developed very high levels of autoantibodies with dominant responses to rat CB11 after CII injections and to rat CB11 and CB9,7 after BII injections. DA (RT1av1) rats developed the most severe arthritis but had only moderate (total) levels of anti-RII IgG: a broad response to CB11, CB10, and CB9,7 after CII injections but predominantly to CB12 and CB9,7 after BII injections. Three RT1n strains--DA.1N(BN), WF.1N(MAXX), and BN--were resistant to BII-induced CIA but developed mild arthritis after immunization with CII. After BII: BN IgG reacted with CB9-7, CB11, and CB12; DA.1N and WF.1N IgG reacted with CB9,7 and CB12. After CII: BN IgG reacted broadly with CB11, CB9-7, CB12, and CB8; WF.1N IgG reacted to CB9-7, CB11, CB8, and CB12; DA.1N IgG reacted with CB8, CB11, and CB9-7. Thus, selective induction of CIA in BN, WF.1N, and DA.1N rats by CII correlated with serum IgG reactivity to rat CB11, but overall strain results identified no single cyanogen-bromide peptide as expressing the sole "arthritogenic" epitope in CIA.

摘要

用天然牛（BII）、猪（PII）或鸡（CII）II型胶原蛋白对7个近交、RT1同源基因大鼠品系进行免疫，并观察关节炎的发病时间、发病率和严重程度。将临床结果与对天然大鼠II型胶原蛋白（RII）以及BII、CII或RII的纯化、复性溴化氰肽具有反应性的IgG进行比较。确定了对RII的CB11、CB9,7和CB12的免疫显性反应。对CB8和CB10也出现了二次反应。在每个品系中定义了可重复的肽反应模式，其反映了RT1和非RT1基因型以及免疫胶原蛋白的种类。BN非RT1基因产物减轻了临床关节炎，但在携带RT1l,n,av1单倍型的三个品系中增加了对CB11的反应水平。WF（RT1u）大鼠易患胶原诱导的关节炎（CIA），在注射CII后产生非常高水平的自身抗体，对大鼠CB11有显性反应，在注射BII后对大鼠CB11和CB9,7有显性反应。DA（RT1av1）大鼠发生最严重的关节炎，但抗RII IgG水平仅为中等（总体）：注射CII后对CB11、CB10和CB9,7有广泛反应，但注射BII后主要对CB12和CB9,7有反应。三个RT1n品系——DA.1N（BN）、WF.1N（MAXX）和BN——对BII诱导的CIA有抗性，但在用CII免疫后发生轻度关节炎。注射BII后：BN IgG与CB9 - 7、CB11和CB12反应；DA.1N和WF.1N IgG与CB9,7和CB12反应。注射CII后：BN IgG与CB11、CB9 - 7、CB12和CB8广泛反应；WF.1N IgG与CB9 - 7、CB11、CB8和CB12反应；DA.1N IgG与CB8。因此，CII在BN、WF.1N和DA.1N大鼠中选择性诱导CIA与血清IgG对大鼠CB11的反应性相关，但总体品系结果未确定单个溴化氰肽表达CIA中唯一的“致关节炎”表位。（注：原文最后“DA.1N IgG reacted with CB8”后面似乎少了内容，已按完整意思翻译）