Longitudinal analysis of Mycobacterium tuberculosis 19-kDa antigen-specific T cells in patients with pulmonary tuberculosis:: association with disease activity and cross-reactivity to a peptide from HIVenv gp120
Longitudinal analysis of Mycobacterium tuberculosis 19-kDa antigen-specific T cells in patients with pulmonary tuberculosis:: association with disease activity and cross-reactivity to a peptide from HIVenv gp120
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DOI：
10.1002/eji.200323480
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发表时间：
2003-06-01
影响因子：
5.4
通讯作者：
Maeurer, MJ
中科院分区：
文献类型：
--
作者：
Höhn, H;Kortsik, C;Maeurer, MJ
CD8(+)T细胞在抗结核分枝杆菌感染的免疫保护中起着核心作用。抗M抗体的靶表位之一。结核分枝杆菌导向的CD8(+)T细胞是人类白细胞抗原A2限制性的19 kDa脂蛋白多肽VLTDGNPPEV。针对这个表位的T细胞克隆不仅识别标称的多肽配体，而且识别HIV包膜gp120(HIVenv Gp120)蛋白中的一个密切相关的多肽(VPTDPNPPEV)，其特征是释放干扰素-γ。这种交叉反应在体外证实了结核分枝杆菌19-kDa四聚体分选的T细胞和HIV+患者的HIVgp120四聚体反应性T细胞。人类白细胞抗原A2(+)感染者(10/10)存在19 kDa抗原反应性T细胞，而正常人(10/10)外周血中无结核分枝杆菌感染。结核分枝杆菌19-kDa抗原反应性T细胞在急性肺结核中升高，随治疗反应而下降(7/10例)，并位于终末分化的CD8(+)T细胞亚群中。识别HIVenv或结核分枝杆菌19 kDa抗原的CD8(+)交叉反应性T细胞可能在同时感染这两种病原体的个体的发病机制中起作用，也可能是活动性结核病的标志。
CD8(+) T cells play a central role in immune protection against infection with Mycobacterium tuberculosis. One of the target epitopes for anti-M. tuberculosis directed CD8(+) T cells is the HLA-A2-restricted 19-kDa lipoprotein peptide VLTDGNPPEV. T cell clones directed against this epitope recognized not only the nominal peptide ligand, but also a closely related peptide (VPTDPNPPEV) from the HIV envelope gp120 (HIVenv gp120) protein characterized by IFN-gamma release. This cross-reactivity was confirmed in ex vivo in M. tuberculosis 19-kDa tetramer-sorted T cells from patients with tuberculosis and in HIVgp120 tetramer-reactive T cells sorted from HIV+ patients. M. tuberculosis 19-kDa antigen-reactive T cells were present in HLA-A2(+) patients (10/10) with HIV infection with no evidence of M. tuberculosis infection, but they are absent in peripheral blood lymphocytes from healthy HLA-A2(+) individuals (10/ 10). M. tuberculosis 19-kDa antigen-reactive T cells were elevated in acute pulmonary tuberculosis, declined with response to therapy (7/10 patients) and resided in the terminally differentiated CD8(+) T cell subset. CD8(+) cross-reactive T cells recognizing HIVenv or M. tuberculosis 19-kDa antigens may contribute to pathogenesis in individuals co-infected with both pathogens and may also present a marker for active tuberculosis.