Hong J, Zang Y C, Tejada-Simon M V, Kozovska M, Li S, Singh R A, Yang D, Rivera V M, Killian J K, Zhang J Z
Multiple Sclerosis Research Laboratory, Department of Neurology, Baylor-Methodist International Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX 77030, USA.
J Immunol. 1999 Sep 15;163(6):3530-8.
T cell responses to the immunodominant peptide (residues 83-99) of myelin basic protein are potentially associated with multiple sclerosis (MS). This study was undertaken to examine whether a common sequence motif(s) exists within the TCR complementarity-determining region (CDR)-3 of T cells recognizing the MBP83-99 peptide. Twenty MBP83-99-reactive T cell clones derived from patients with MS were analyzed for CDR3 sequences, which revealed several shared motifs. Some V beta 13.1 T cell clones derived from different patients with MS were found to contain an identical CDR3 motif, V beta 13.1-LGRAGLTY. Oligonucleotides complementary to the shared CDR3 motifs were used as specific probes to detect identical target CDR3 sequences in a large panel of T cell lines reactive to MBP83-99 and unprimed PBMC. The results revealed that, in contrast to other CDR3 motifs examined, the LGRAGLTY motif was common to T cells recognizing the MBP83-99 peptide, as evident by its expression in the majority of MBP83-99-reactive T cell lines (36/44) and PBMC specimens (15/48) obtained from randomly selected MS patients. The motif was also detected in lower expression in some PBMC specimens from healthy individuals, suggesting the presence of low precursor frequency of T cells expressing this motif in healthy individuals. This study provides new evidence indicating that the identified LGRAGLTY motif is preferentially expressed in MBP83-99-reactive T cells. The findings have important implications in monitoring and targeting MBP83-99-reactive T cells in MS.
T细胞对髓鞘碱性蛋白免疫显性肽（第83 - 99位氨基酸残基）的反应可能与多发性硬化症（MS）相关。本研究旨在检测识别MBP83 - 99肽的T细胞的T细胞受体互补决定区（CDR）-3内是否存在共同的序列基序。对20个源自MS患者的MBP83 - 99反应性T细胞克隆进行了CDR3序列分析，结果显示了几个共享基序。发现一些源自不同MS患者的Vβ13.1 T细胞克隆含有相同的CDR3基序，即Vβ13.1 - LGRAGLTY。与共享的CDR3基序互补的寡核苷酸被用作特异性探针，以检测大量对MBP83 - 99有反应的T细胞系和未致敏外周血单个核细胞（PBMC）中相同的目标CDR3序列。结果显示，与所检测的其他CDR3基序不同，LGRAGLTY基序在识别MBP83 - 99肽的T细胞中很常见，这在大多数MBP83 - 99反应性T细胞系（36/44）和从随机选择的MS患者获得的PBMC标本（15/48）中的表达中得到了证实。在一些健康个体的PBMC标本中也检测到该基序，但表达水平较低，这表明健康个体中表达该基序的T细胞前体频率较低。本研究提供了新的证据，表明所鉴定的LGRAGLTY基序在MBP83 - 99反应性T细胞中优先表达。这些发现对监测和靶向MS中MBP83 - 99反应性T细胞具有重要意义。
