Zang Y C, Hong J, Rivera V M, Killian J, Zhang J Z
Multiple Sclerosis Research Laboratory, Department of Neurology and Baylor-Methodist Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX 77030, USA.
J Immunol. 2000 Apr 15;164(8):4011-7. doi: 10.4049/jimmunol.164.8.4011.
T cell responses to myelin basic protein (MBP) are potentially involved in the pathogenesis of multiple sclerosis (MS). Immunization with irradiated MBP-reactive T cells (T cell vaccination) induces anti-idiotypic T cell responses that suppress circulating MBP-reactive T cells. This T cell-T cell interaction is thought to involve the recognition of TCR expressed on target T cells. The study was undertaken to define the idiotypic determinants responsible for triggering CD8+ cytotoxic anti-idiotypic T cell responses by T cell vaccination in patients with MS. A panel of 9-mer synthetic TCR peptides corresponding to complementarity-determining region 2 (CDR2) and CDR3 of the immunizing MBP-reactive T cell clones were used to isolate anti-idiotypic T cell lines from immunized MS patients. The resulting TCR-specific T cell lines expressed exclusively the CD8 phenotype and recognized preferentially the CDR3 peptides. CDR3-specific T cell lines were found to lyze specifically autologous immunizing MBP-reactive T cell clones. The findings suggest that CDR3-specific T cells represented anti-idiotypic T cell population induced by T cell vaccination. In contrast, the CDR2 peptides were less immunogenic and contained cryptic determinants as the CDR2-specific T cell lines did not recognize autologous immunizing T cell clones from which the peptide sequence was derived. The study has important implications in our understanding of in vivo idiotypic regulation of autoimmune T cells and the regulatory mechanism underlying T cell vaccination.
T细胞对髓鞘碱性蛋白（MBP）的反应可能参与了多发性硬化症（MS）的发病机制。用经辐照的MBP反应性T细胞进行免疫接种（T细胞疫苗接种）可诱导抗独特型T细胞反应，从而抑制循环中的MBP反应性T细胞。这种T细胞与T细胞的相互作用被认为涉及对靶T细胞上表达的TCR的识别。本研究旨在确定在MS患者中通过T细胞疫苗接种触发CD8+细胞毒性抗独特型T细胞反应的独特型决定簇。使用一组与免疫MBP反应性T细胞克隆的互补决定区2（CDR2）和CDR3相对应的9聚体合成TCR肽，从免疫的MS患者中分离抗独特型T细胞系。所得的TCR特异性T细胞系仅表达CD8表型，并优先识别CDR3肽。发现CDR3特异性T细胞系可特异性裂解自体免疫MBP反应性T细胞克隆。这些发现表明，CDR3特异性T细胞代表了由T细胞疫苗接种诱导的抗独特型T细胞群体。相比之下，CDR2肽的免疫原性较低，并且含有隐蔽决定簇，因为CDR2特异性T细胞系不能识别其肽序列所源自的自体免疫T细胞克隆。该研究对于我们理解自身免疫性T细胞的体内独特型调节以及T细胞疫苗接种的调节机制具有重要意义。
