Yasuoka Hidekata, Okazaki Yuka, Kawakami Yutaka, Hirakata Michito, Inoko Hidetoshi, Ikeda Yasuo, Kuwana Masataka
Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Arthritis Rheum. 2004 Nov;50(11):3658-62. doi: 10.1002/art.20597.
To detect and characterize the autoreactive CD8+ T cells to major histocompatibility complex class I chain-related gene A (MICA), a stress-inducible antigen preferentially expressed on the epithelium and endothelium, in patients with Behcet's disease (BD).
A candidate for the antigenic MICA peptide was selected based on its predicted binding affinity for HLA-B51 and proteasomal cleavage sites. Peripheral blood T cells from 14 patients with BD and 15 healthy controls were repeatedly stimulated with the MICA peptide, and the specific T cell response was measured by peptide-induced interferon-gamma. Cytotoxic T lymphocyte activity was examined by chromium-51 release from an HLA-B51-transfected B cell line in the presence of the MICA peptide.
A 9-mer peptide AAAAAIFVI (termed MICA transmembrane [MICA-TM]) was selected as a candidate for the antigenic peptide presented by HLA-B51. A specific T cell response to MICA-TM was detected in 4 patients with BD (29%) but in none of the 15 healthy donors. All 4 responders had HLA-B51 and active disease, and the specific T cell response was lost after the BD-related symptoms disappeared. The MICA-induced T cell response was specifically inhibited by anti-HLA class I antibody or by CD8+ cell depletion. MICA-reactive T cells recognized an HLA-B51-transfected B cell line pulsed with MICA-TM or a B cell line transfected with both HLA-B51 and MICA in the absence of exogenous peptides. Finally, MICA-stimulated T cell lines lysed the HLA-B51-expressing B cell line in the presence of MICA-TM.
HLA-B51-restricted cytotoxic T lymphocytes autoreactive to MICA may be involved in the pathogenesis of BD.
检测和鉴定白塞病（BD）患者中针对主要组织相容性复合体I类链相关基因A（MICA）的自身反应性CD8 + T细胞。MICA是一种应激诱导抗原，优先表达于上皮和内皮细胞。
根据预测的与HLA - B51的结合亲和力和蛋白酶体切割位点，选择抗原性MICA肽的候选物。用MICA肽反复刺激14例BD患者和15例健康对照的外周血T细胞，并通过肽诱导的干扰素-γ测量特异性T细胞反应。在存在MICA肽的情况下，通过从HLA - B51转染的B细胞系中释放51铬来检测细胞毒性T淋巴细胞活性。
选择9聚体肽AAAAAIFVI（称为MICA跨膜区[MICA - TM]）作为由HLA - B51呈递的抗原肽的候选物。在4例BD患者（29%）中检测到对MICA - TM的特异性T细胞反应，但在15例健康供体中均未检测到。所有4例反应者均具有HLA - B51且患有活动性疾病，并且在BD相关症状消失后特异性T细胞反应消失。MICA诱导的T细胞反应被抗HLA I类抗体或CD8 +细胞耗竭特异性抑制。MICA反应性T细胞识别用MICA - TM脉冲处理的HLA - B51转染的B细胞系或在没有外源性肽的情况下同时转染HLA - B51和MICA的B细胞系。最后，MICA刺激的T细胞系在存在MICA - TM的情况下裂解表达HLA - B51的B细胞系。
对MICA具有自身反应性的HLA - B51限制性细胞毒性T淋巴细胞可能参与BD的发病机制。
