Identification of HLA‐DRB1*09:01‐restricted Mycobacterium tuberculosis CD4+ T‐cell epitopes
Identification of HLA‐DRB1*09:01‐restricted Mycobacterium tuberculosis CD4+ T‐cell epitopes
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DOI：
10.1002/1873-3468.12478
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发表时间：
2016-11
期刊：
影响因子：
3.5
通讯作者：
Sudong Liu;Shimeng Zhang;Hui Wang;Jianchun He;Xiao‐Fan Yang;Xialin Du;Li Ma
中科院分区：
文献类型：
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作者：
Sudong Liu;Shimeng Zhang;Hui Wang;Jianchun He;Xiao‐Fan Yang;Xialin Du;Li Ma
CD 4 + T细胞在预防结核分枝杆菌（MTB）感染中起着重要作用。我们鉴定了三个HLA-DRB 1 *09：01限制性CD 4 + T细胞表位，其来源于显性分泌型MTB抗原38 kDa（Rv 3804 c）和Ag 85 A（Rv 0934）。通过计算机预测程序和TB患者外周血单核细胞（PBMC）中IFN-γ诱导分析筛选抗原的表位。为了响应来自38 kDa和Ag 85 A的三种高亲和力预测表位，刺激来自HLA-DRB 1 *09：01 TB患者的CD 4 + T细胞产生IFN-γ和肿瘤坏死因子（TNF）-α。通过羧基荧光素琥珀酰亚胺酯稀释试验，还发现三种表位诱导CD 4 + T细胞增殖。这些HLA-DRB 1 *09：01限制性CD 4 + T细胞表位有助于分析38 kDa和Ag 85 A特异性T细胞在结核分枝杆菌感染中的作用，并为结核病疫苗的设计铺平了道路。
CD4+ T cells play an essential role in protection against Mycobacterium tuberculosis (MTB) infection. We identified three HLA‐DRB1*09:01‐restricted CD4+ T‐cell epitopes derived from the dominant secreted MTB antigens 38 kDa (Rv3804c) and Ag85A (Rv0934). The antigens were screened for epitopes by in silico prediction programs and analysis of IFN‐γ induction in the peripheral blood mononuclear cells (PBMCs) from TB patients. In response to three of the high‐affinity predicted epitopes derived from 38 kDa and Ag85A, CD4+ T cells from HLA‐DRB1*09:01 TB patients were stimulated to produce IFN‐γ and Tumor Necrosis Factor (TNF)‐α. The three epitopes were also found to induce the proliferation of CD4+ T cells by carboxyfluorescein succinimidyl ester‐diluted assays. These HLA‐DRB1*09:01‐restricted CD4+ T‐cell epitopes facilitate analysis of the role of 38 kDa‐ and Ag85A‐specific T cells in MTB infection and pave way for the design of vaccines against tuberculosis.