Cremer M A, Terato K, Watson W C, Griffiths M M, Townes A S, Kang A H
Research Service, Veterans Administration Medical Center, Memphis, TN.
J Immunol. 1992 Aug 1;149(3):1045-53.
To determine the number and location of antibody binding epitopes on type II collagen, outbred and inbred rats were immunized with chick, bovine, human, and rat type II collagen (CII, BII, HII, and RII); all sera were assayed for reaction with a panel of CB peptides purified and renatured from the immunizing collagen and from RII. Antibody reaction patterns (profiles) varied among individual outbred rats but were essentially constant over time and changed little after boosting. The strongest antibody reactions were to CB11, CB9-7, and CB12 followed by CB8, CB10, and CB6. Antibody profiles varied depending on the species of collagen used for immunization and the strain of rat immunized. Except for CB10, where antibodies were largely specific for heterologous collagens, antibodies reactive with all other CB peptides cross-reacted strongly with renatured rat CB peptides. Sera from inbred BB rats immunized with BII, CII, or HII reacted best with CB11, unlike antisera to RII that reacted strongly with CB9-7. Inbred LEW, COP, WKY, F344, and BUF rats immunized with BII reacted strongest with CB9-7 and variably with CB11 and CB12. BBxLEW F1 hybrid rats reacted almost equally with CB11 and CB9-7 producing an antibody profile intermediate to those elicited in the parent strains. Finally, antibodies reactive with rat CB11, CB9-7, and CB12 could be eluted from normal rat cartilage incubated in anti-BII serum; antibody eluate profiles generally paralleled the profile produced by the sera applied to cartilage. Taken together, these findings indicate that multiple antibody-reactive epitopes on type II collagen may be instrumental in the initiation of collagen-induced arthritis in rats, particularly shared or cross-reactive epitopes located within CB11, CB9-7, CB12, and CB8.
为了确定抗II型胶原抗体结合表位的数量和位置，用鸡、牛、人及大鼠II型胶原（CII、BII、HII和RII）对远交系和近交系大鼠进行免疫；检测所有血清与一组从免疫用胶原和RII中纯化并复性的CB肽的反应。抗体反应模式（图谱）在个体远交系大鼠之间存在差异，但随时间基本恒定，再次免疫后变化不大。最强的抗体反应针对CB11、CB9 - 7和CB12，其次是CB8、CB10和CB6。抗体图谱因用于免疫的胶原种类和免疫大鼠的品系而异。除CB10外，针对该肽段的抗体主要对异源胶原具有特异性，与所有其他CB肽反应的抗体与复性的大鼠CB肽有强烈交叉反应。用BII、CII或HII免疫的近交系BB大鼠的血清与CB11反应最佳，而与RII免疫产生的抗血清不同，后者与CB9 - 7反应强烈。用BII免疫的近交系LEW、COP、WKY、F344和BUF大鼠与CB9 - 7反应最强，与CB11和CB12反应程度不一。BBxLEW F1杂种大鼠与CB11和CB9 - 7的反应几乎相同，产生的抗体图谱介于亲本品系所诱导的图谱之间。最后，与大鼠CB11、CB9 - 7和CB12反应的抗体可从在抗BII血清中孵育的正常大鼠软骨中洗脱；抗体洗脱图谱通常与应用于软骨的血清所产生的图谱平行。综上所述，这些发现表明II型胶原上多个抗体反应性表位可能在大鼠胶原诱导性关节炎的起始中起作用，特别是位于CB11、CB9 - 7、CB12和CB8内的共享或交叉反应性表位。
