Mycobacterium tuberculosis genome-wide screen exposes multiple CD8+ T cell epitopes
Mycobacterium tuberculosis genome-wide screen exposes multiple CD8+ T cell epitopes
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DOI：
10.1111/j.1365-2249.2005.02751.x
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发表时间：
2005-04-01
影响因子：
4.6
通讯作者：
Brookes, RH
中科院分区：
文献类型：
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作者：
Hammond, AS;Klein, MR;Brookes, RH
越来越多的证据表明人类白细胞抗原（HLA）I类限制性CD 8（+）T细胞在抗结核病的保护性免疫中发挥作用，但相对较少的表位特异性的病原体，结核分枝杆菌，报告。这里是M的全基因组筛选。结核病的HLA-B*3501 T细胞表位的鉴定。在479个预测表位中，合成了13个得分最高的表位，并用于在干扰素（IFN）-γ的培养和离体酶联免疫斑点（ELISPOT）测定中再刺激来自自然暴露的HLA-B*3501健康个体的淋巴细胞。所有13种肽引起的反应在个体之间差异很大。对于三种肽，扩增了CD 8（+）T细胞系，并且13种中的4种通过HLA-B7超型家族被允许识别。虽然还需要进一步的测试，我们显示全基因组筛选是可行的未知的分枝杆菌抗原参与对自然感染的免疫力的鉴定。而抗M.尽管结核病感染仍不清楚，但常规I类限制性CD 8（+）T细胞应答似乎在整个基因组中广泛存在。
Mounting evidence suggests human leucocyte antigen (HLA) class I-restricted CD8(+) T cells play a role in protective immunity against tuberculosis yet relatively few epitopes specific for the causative organism, Mycobacterium tuberculosis, are reported. Here a total genome-wide screen of M. tuberculosis was used to identify putative HLA-B*3501 T cell epitopes. Of 479 predicted epitopes, 13 with the highest score were synthesized and used to restimulate lymphocytes from naturally exposed HLA-B*3501 healthy individuals in cultured and ex vivo enzyme-linked immunospot (ELISPOT) assays for interferon (IFN)-gamma. All 13 peptides elicited a response that varied considerably between individuals. For three peptides CD8(+) T cell lines were expanded and four of the 13 were recognized permissively through the HLA-B7 supertype family. Although further testing is required we show the genome-wide screen to be feasible for the identification of unknown mycobacterial antigens involved in immunity against natural infection. While the mechanisms of protective immunity against M. tuberculosis infection remain unclear, conventional class I-restricted CD8(+) T cell responses appear to be widespread throughout the genome.