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[目的]研究1型糖尿病相关的胰岛素原(Proinsulin,PI)T细胞表位。[方法]采用有限稀释法建立糖尿病病人胰岛素原抗原特异性的T细胞克隆,~(51)Cr释放细胞毒性试验测定T细胞激活的HLA限制性和PI肽段中最小的抗原表位,用流式细胞仪分析其表型及表面肿瘤坏死因子凋亡诱导配体(tumor necrosis factor-related apopto-sis-inducing ligand,TRAIL)的表达。[结果]建立了PI抗原特异性的CD4~+ T细胞克隆TWHPI-1,CD8~+ T细胞克隆TWH PI-2。前者为HLA DRB4 0101限制,PI最小抗原表位在PI(79~87),74.2%细胞表达 TRAIL。后者为HLA A1限制。PI最小抗原表位在PI(78~86),94.9%细胞表达TRAIL。[结论]HLA DRB4 0101-Al可能参与IDDM的致病过程,TRAIL可能是两株T细胞克隆引起胰岛细胞死亡的因子之一。
[Objective] To study the type 1 diabetes-related proinsulin (PI) T cell epitopes. [Method] T-cell clones specific to proinsulin antigen of diabetic patients were established by limiting dilution method, and HLA-restricted HLA-restricted T cells and the smallest epitope of PI peptide were measured by ~ (51) Cr release cytotoxicity assay. Cytometry was used to analyze the phenotype and the expression of tumor necrosis factor-related apopto-sis-inducing ligand (TRAIL). [Results] The PI antigen specific CD4 ~ + T cell clone TWHPI-1 and CD8 ~ + T cell clone TWH PI-2 were established. The former is limited by HLA DRB4 0101, PI minimum epitopes in PI (79 ~ 87), 74.2% cells express TRAIL. The latter is HLA A1 restriction. PI minimal epitope in PI (78 ~ 86), 94.9% cells express TRAIL. [Conclusion] HLA DRB4 0101-Al may be involved in the pathogenesis of IDDM. TRAIL may be one of the factors that cause the death of islet cells by two T cell clones.