Myers L K, Rosloniec E F, Seyer J M, Stuart J M, Kang A H
Department of Pediatrics, University of Tennessee, Memphis 38163.
J Immunol. 1993 May 15;150(10):4652-8.
The immunization of genetically susceptible strains of mice with type II collagen (CII) elicits a collagen-induced arthritis that resembles rheumatoid arthritis. Our laboratory previously identified a region of CII, CII-245-270, that contains a T cell epitope that is prominent in the immune response to CII. Residues critical to the I-Aq-restricted presentation of this determinant have been characterized. To produce synthetic peptides with the potential of disrupting I-Aq-restricted Ag presentation, synthetic analogue peptides were developed that contain site-directed substitutions in critical positions. One analogue peptide was found to be an efficient competitor for binding to I-Aq and to be capable of inhibiting T cell responses in vitro. When DBA/1 mice were coimmunized with CII and the analogue peptide, the incidence and severity of arthritis were greatly reduced, concordant with the humoral immune responses to CII.
用II型胶原（CII）对基因易感的小鼠品系进行免疫接种会引发一种类似于类风湿性关节炎的胶原诱导性关节炎。我们实验室之前鉴定出CII的一个区域，即CII-245-270，该区域包含一个T细胞表位，在对CII的免疫反应中很突出。对该决定簇的I-Aq限制性呈递至关重要的残基已得到表征。为了生产具有破坏I-Aq限制性抗原呈递潜力的合成肽，开发了在关键位置含有定点取代的合成类似肽。发现一种类似肽是与I-Aq结合的有效竞争者，并且能够在体外抑制T细胞反应。当用CII和类似肽对DBA/1小鼠进行联合免疫接种时，关节炎的发病率和严重程度大大降低，这与对CII的体液免疫反应一致。
