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首页> 外文期刊>Infection and immunity >T-Cell Recognition of the HspX Protein of Mycobacterium tuberculosis Correlates with Latent M. tuberculosis Infection but Not with M. bovis BCG Vaccination
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T-Cell Recognition of the HspX Protein of Mycobacterium tuberculosis Correlates with Latent M. tuberculosis Infection but Not with M. bovis BCG Vaccination

机译：结核分枝杆菌HspX蛋白的T细胞识别与潜在的结核分枝杆菌感染有关，但与牛分枝杆菌BCG疫苗接种无关

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During stationary growth or in vitro conditions mimicking relevant aspects of latency, the HspX protein (Rv2031c) is specifically upregulated by Mycobacterium tuberculosis. In this study we compared T-cell responses against HspX and the secreted M. tuberculosis protein Ag85B (Rv1886c) in tuberculosis (TB) patients, tuberculin skin test-positive individuals, M. bovis BCG-vaccinated individuals, and healthy negative controls. Gamma interferon responses to HspX were significantly higher in M. tuberculosis-exposed individuals than in M. tuberculosis-unexposed BCG vaccinees. In contrast, no such differences were found with respect to T-cell responses against Ag85B. Therefore, BCG-based vaccines containing relevant fragments of HspX may induce improved responses against this TB latency antigen. To identify relevant major histocompatibility complex class I- and class II-restricted HspX-specific T-cell epitopes, we immunized HLA-A2/Kb and HLA-DR3.Ab0 transgenic (tg) mice with HspX. Two new T-cell epitopes were identified, p91-105 and p31-50, restricted via HLA-A*0201 and HLA-DRB1*0301, respectively. These epitopes were recognized by human T cells as well, underlining the relevance of HspX T-cell recognition both in vivo and in vitro. In line with the data in humans, BCG immunization of both tg strains did not lead to T-cell responses against HspX-derived epitopes, whereas nonlatency antigens were efficiently recognized. These data support the notion that BCG vaccination per se does not induce T-cell responses against the latency antigen, HspX. Thus, we suggest that subunit vaccines incorporating HspX and/or other latency antigens, as well as recombinant BCG strains expressing latency antigens need to be considered as new vaccines against TB.
机译：在静止生长或模仿潜伏期相关方面的体外条件下，HspX蛋白（Rv2031c）被结核分枝杆菌特异性上调。在这项研究中，我们比较了针对HspX和分泌的 M的T细胞反应。结核病（TB）患者，结核菌素皮肤试验阳性个体 M的结核菌素蛋白Ag85B（Rv1886c）。牛BCG疫苗接种的个体和健康的阴性对照。在 M中，γ干扰素对HspX的反应明显更高。肺结核暴露的个体比 M。结核未暴露的卡介苗疫苗。相反，在针对Ag85B的T细胞应答方面未发现此类差异。因此，含有HspX相关片段的基于BCG的疫苗可能会诱导针对此TB潜伏期抗原的改良反应。为了鉴定相关的主要组织相容性复杂的I类和II类限制性HspX特异性T细胞表位，我们免疫了HLA-A2 / K b 和HLA-DR3.Ab 0 具有HspX的转基因（tg）小鼠。鉴定出两个新的T细胞表位，p91-105和p31-50，分别受HLA-A * 0201和HLA-DRB1 * 0301限制。这些表位也可以被人T细胞识别，这突显了HspX T细胞识别在体内和体外的相关性。与人类数据一致，两种tg菌株的BCG免疫接种均不会导致针对HspX衍生抗原决定簇的T细胞应答，而非潜伏期抗原则得到了有效识别。这些数据支持BCG疫苗接种本身不会诱导针对潜伏期抗原HspX的T细胞反应的观点。因此，我们建议需要将掺入HspX和/或其他潜伏期抗原的亚单位疫苗以及表达潜伏期抗原的重组BCG菌株视为抗结核新疫苗。

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