Malmström V, Kjellén P, Holmdahl R
Department of Cell & Molecular Biology, Lund University, Sweden.
J Autoimmun. 1998 Jun;11(3):213-21. doi: 10.1006/jaut.1998.0198.
T cell recognition of type II collagen (CII) is a crucial event in the induction of collagen-induced arthritis in the mouse. Several CII peptides have been shown to be of importance, dependent on which MHC haplotype the mouse carries. By sequencing the rat CII and comparing the sequence with mouse, human, bovine and chicken CII, we have found that the immunodominant peptides all differ at critical positions compared with the autologous mouse sequence. Transgenic expression of the immunodominant Aq-restricted heterologous CII 256-270 epitope inserted into type I collagen (TSC mice) or type II collagen (MMC-1 mice) led to epitope-specific tolerance. Immunization of TSC mice with chick CII led to arthritis and immune responses, dependent on the subdominant, Aq-restricted and chick-specific CII 190-200 epitope. Immunization of F1 mice, expressing both H-2q and H-2r as well as transgenic expression of the Aq-restricted CII 256-270 epitope in cartilage, with bovine CII, led to arthritis, dependent on the Ar-restricted, bovine-specific epitope CII 607-621. These data show that the immunodominance of CII recognition is directed towards heterologous determinants, and that T cells directed towards the corresponding autologous epitopes are tolerated without evidence of active suppression.
T细胞对II型胶原蛋白（CII）的识别是小鼠胶原诱导性关节炎发生过程中的关键事件。已证明几种CII肽很重要，这取决于小鼠所携带的MHC单倍型。通过对大鼠CII进行测序并将其序列与小鼠、人类、牛和鸡的CII进行比较，我们发现与自体小鼠序列相比，免疫显性肽在关键位置均存在差异。将免疫显性的Aq限制性异源CII 256 - 270表位转基因表达插入I型胶原蛋白（TSC小鼠）或II型胶原蛋白（MMC - 1小鼠）中可导致表位特异性耐受。用鸡CII免疫TSC小鼠会引发关节炎和免疫反应，这取决于次显性的、Aq限制性且鸡特异性的CII 190 - 200表位。对同时表达H - 2q和H - 2r以及在软骨中Aq限制性CII 256 - 270表位转基因表达的F1小鼠用牛CII进行免疫，会引发关节炎，这取决于Ar限制性、牛特异性表位CII 607 - 621。这些数据表明，CII识别的免疫显性针对的是异源决定簇，并且针对相应自体表位的T细胞处于耐受状态，没有证据表明存在主动抑制。
