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人类T细胞克隆识别在大肠杆菌中表达的一种主要麻风杆菌蛋白抗原。

Human T-cell clones recognize a major M. leprae protein antigen expressed in E. coli.

作者信息

Mustafa A S, Gill H K, Nerland A, Britton W J, Mehra V, Bloom B R, Young R A, Godal T

出版信息

Nature. 1986;319(6048):63-6. doi: 10.1038/319063a0.

Abstract

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. As with other intracellular parasites, protective immunity is dependent on T cells and cell-mediated immunity. In animal models, immunization with killed armadillo-derived M. leprae elicits strong T-cell responses, delayed-type hypersensitivity and protection against viable challenge. We have recently shown that killed M. leprae can induce delayed-type hypersensitivity in healthy human volunteers. Identification of the M. leprae antigens that are recognized by T cells and may be involved in protection has been hampered by the inability to cultivate the organism in vitro and by difficulties in antigen purification from limited quantities of armadillo-derived bacillus. Because genes for the major protein antigens of M. leprae as seen by mouse monoclonal antibodies have been isolated, it has become possible to test whether these individual antigens are recognized by T cells. We screened crude lambda gtll phage lysates of Escherichia coli containing individual M. leprae antigens using M. leprae-specific T-cell clones isolated from M. leprae-vaccinated volunteers. Using this method, we find that nearly half of the M. leprae-specific T-cell clones are stimulated to proliferate by lysates containing an epitope of a M. leprae protein of relative molecular mass 18,000 (18K).

摘要

麻风病是一种由麻风分枝杆菌引起的慢性传染病。与其他细胞内寄生虫一样,保护性免疫依赖于T细胞和细胞介导的免疫。在动物模型中,用杀死的犰狳源麻风分枝杆菌进行免疫可引发强烈的T细胞反应、迟发型超敏反应,并对活的攻击具有保护作用。我们最近发现,杀死的麻风分枝杆菌可在健康人类志愿者中诱导迟发型超敏反应。由于无法在体外培养该生物体,且从有限数量的犰狳源杆菌中纯化抗原存在困难,因此对被T细胞识别且可能参与保护作用的麻风分枝杆菌抗原的鉴定受到了阻碍。由于已分离出小鼠单克隆抗体所识别的麻风分枝杆菌主要蛋白质抗原的基因,因此有可能测试这些单个抗原是否能被T细胞识别。我们使用从接种过麻风分枝杆菌的志愿者中分离出的麻风分枝杆菌特异性T细胞克隆,筛选了含有单个麻风分枝杆菌抗原的大肠杆菌粗λgtll噬菌体裂解物。使用这种方法,我们发现近一半的麻风分枝杆菌特异性T细胞克隆会被含有相对分子质量为18000(18K)的麻风分枝杆菌蛋白表位的裂解物刺激而增殖。

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