Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Behcet's disease
Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Behcet's disease
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DOI：
10.1002/art.20597
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发表时间：
2004-11-01
影响因子：
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通讯作者：
Kuwana, M
中科院分区：
文献类型：
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作者：
Yasuoka, H;Okazaki, Y;Kuwana, M
Objective.目的检测白塞病（BD）患者外周血CD 8 + T细胞对主要组织相容性复合物I类链相关基因A（云母）的反应性，并探讨其特征。基于其对HLA-B51和蛋白酶体切割位点的预测结合亲和力选择抗原性云母肽的候选物。用云母肽反复刺激来自14名BD患者和15名健康对照的外周血T细胞，并通过肽诱导的干扰素-γ测量特异性T细胞应答。在云母肽存在的情况下，通过HLA-B51转染的B细胞系释放铬-51来检查细胞毒性T淋巴细胞活性。结果。选择9-mer肽AAAAAIFVI（称为云母跨膜[MICA-TM]）作为HLA-B51呈递的抗原肽的候选物。在4名BD患者（29%）中检测到对MICA-TM的特异性T细胞反应，但在15名健康捐赠者中均未检测到。所有4名应答者均具有HLA-B51和活动性疾病，并且在BD相关症状消失后丧失了特异性T细胞应答。MICA诱导的T细胞应答被抗HILA I类抗体或CD 8+细胞耗竭特异性抑制。MICA反应性T细胞识别用MICA-TM脉冲的HLA-B51转染的B细胞系或在不存在外源肽的情况下用HLA-B51和云母两者转染的B细胞系。最后，在MICA-TM存在下，MICA刺激的T细胞系溶解表达HLA-B51的B细胞系。对云母反应的HLA-B51限制性细胞毒性T淋巴细胞可能参与BD的发病。
Objective. 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).Methods. 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.Results. 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-HILA 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.Conclusion. HLA-B51-restricted cytotoxic T lymphocytes autoreactive to MICA may be involved in the pathogenesis of BD.