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结核分枝杆菌10千道尔顿抗原的免疫反应性

Immunoreactivity of a 10-kDa antigen of Mycobacterium tuberculosis.

作者信息

Barnes P F, Mehra V, Rivoire B, Fong S J, Brennan P J, Voegtline M S, Minden P, Houghten R A, Bloom B R, Modlin R L

机构信息

Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.

出版信息

J Immunol. 1992 Mar 15;148(6):1835-40.

PMID:1371791
Abstract

Identification of Ag of Mycobacterium tuberculosis recognized by T cells is essential to understanding the pathogenesis of tuberculosis and mechanism(s) of resistance to infection. Previous studies evaluating the immunoreactivity of nitrocellulose transfers of M. tuberculosis Ag separated by SDS-PAGE indicated that a high proportion of M. tuberculosis-reactive T cell lines proliferate in response to a 10-kDa Ag. We therefore purified this Ag from M. tuberculosis culture filtrates and evaluated its immunoreactivity in patients with tuberculous infection. Proliferative responses of PBMC to the 10-kDa Ag were similar to those induced by whole M. tuberculosis and greater than those elicited by other proteins isolated from culture filtrate. Furthermore, in patients with tuberculous pleuritis, proliferative responses to the 10-kDa Ag were higher in pleural fluid mononuclear cells than in PBMC, indicating that T cell reactivity to this Ag is enhanced at the site of disease. The first 15 amino acids of the 10-kDa Ag were identical to those defined previously for Bacillus Calmette-Guérin-a (BCG-a), and a T cell clone recognized the 10-kDa Ag and a peptide of BCG-a, indicating that the 10-kDa Ag corresponds to BCG-a. This Ag elicited IFN-gamma production by pleural fluid mononuclear cells and by PBMC from healthy tuberculin reactors, suggesting that the 10-kDa Ag can enhance macrophage activation and resistance to mycobacterial infection. Our findings indicate that the 10-kDa Ag of M. tuberculosis is highly immunoreactive and should be evaluated for its capacity to elicit protective immunity.

摘要

鉴定被T细胞识别的结核分枝杆菌抗原对于理解结核病发病机制和抗感染机制至关重要。先前评估经SDS-PAGE分离的结核分枝杆菌抗原的硝酸纤维素转移膜免疫反应性的研究表明,高比例的结核分枝杆菌反应性T细胞系对一种10 kDa抗原产生增殖反应。因此,我们从结核分枝杆菌培养滤液中纯化了该抗原,并评估了其在结核感染患者中的免疫反应性。外周血单核细胞(PBMC)对10 kDa抗原的增殖反应与全结核分枝杆菌诱导的反应相似,且大于从培养滤液中分离的其他蛋白质所引发的反应。此外,在结核性胸膜炎患者中,胸腔积液单核细胞对10 kDa抗原的增殖反应高于PBMC,表明T细胞对该抗原的反应性在疾病部位增强。10 kDa抗原的前15个氨基酸与先前确定的卡介苗-a(BCG-a)的氨基酸相同,并且一个T细胞克隆识别10 kDa抗原和BCG-a的一种肽,表明10 kDa抗原对应于BCG-a。该抗原可诱导胸腔积液单核细胞和健康结核菌素反应者的PBMC产生γ干扰素,提示10 kDa抗原可增强巨噬细胞活化和对分枝杆菌感染的抵抗力。我们的研究结果表明,结核分枝杆菌的10 kDa抗原具有高度免疫反应性,应评估其引发保护性免疫的能力。

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