Celiac disease association with CD8+ T cell responses:: Identification of a novel gliadin-derived HLA-A2-restricted epitope
Celiac disease association with CD8+ T cell responses:: Identification of a novel gliadin-derived HLA-A2-restricted epitope
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DOI：
10.4049/jimmunol.170.5.2719
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发表时间：
2003-03-01
影响因子：
4.4
通讯作者：
Sette, A
中科院分区：
文献类型：
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作者：
Gianfrani, C;Troncone, R;Sette, A
与乳糜泻相关的组织学病变的诊断标志之一是抗原特异性未知的CD 8（+）T细胞广泛浸润小肠上皮。在这项研究中，我们报告识别麦醇溶蛋白衍生肽（A-麦醇溶蛋白123-132）的CD 8（+）T淋巴细胞从腹腔患者。A-麦醇溶蛋白123-132特异性IFN-γ产生和细胞毒性活性在来自无麸质饮食患者的PBMC中检测到，但在来自含麸质饮食的乳糜泻患者或健康对照的PBMC中未检测到。相反，A-麦醇溶蛋白123-132特异性细胞分离自无麸质或含麸质饮食的患者的小肠活检。来源于小肠粘膜并且对123-132表位具有特异性的短期T细胞系识别用完整重组α-麦醇溶蛋白或部分胃蛋白酶-胰蛋白酶麦醇溶蛋白消化物脉冲的人APC。最后，我们推测一种可能的机制，导致加工和介绍I类限制性麦醇溶蛋白衍生的表位在乳糜泻患者。
One of the diagnostic hallmarks of the histological lesions associated with celiac disease is the extensive infiltration of the small intestinal epithelium by CD8(+) T cells of unknown Ag specificity. In this study, we report recognition of the gliadin-derived peptide (A-gliadin 123-132) by CD8(+) T lymphocytes from celiac patients. A-gliadin 123-132-specific IFN-gamma production and cytotoxic activity were detected in PBMCs derived from patients on gluten-free diet, but not from either celiac patients on gluten-containing diet or healthy controls. In contrast, A-gliadin 123-132-specific cells were isolated from small intestine biopsies of patients on either gluten-free or gluten-containing diets. Short-term T cell lines derived from the small intestinal mucosa and specific for the 123-132 epitope recognized human APC pulsed with either whole recombinant a-gliadin or a partial pepsin-trypsin gliadin digest. Finally, we speculate on a possible mechanism leading to processing and presentation of class I-restricted gliadin-derived epitopes in celiac disease patients.