T lymphocytes from healthy individuals with specificity to self-epitopes shared by the mycobacterial and human 65-kilodalton heat shock protein.
T lymphocytes from healthy individuals with specificity to self-epitopes shared by the mycobacterial and human 65-kilodalton heat shock protein.
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DOI：
10.4049/jimmunol.143.9.2844
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发表时间：
1989-11
影响因子：
4.4
通讯作者：
M. E. Munk;B. Schoel;S. Modrow;R. Karr;Richard A. Young;Stefan H. E. Kaufmann
中科院分区：
文献类型：
--
作者：
M. E. Munk;B. Schoel;S. Modrow;R. Karr;Richard A. Young;Stefan H. E. Kaufmann
对分枝杆菌病原体的免疫应答包括相当大比例的T细胞，它们对65 kda的热休克蛋白（hsp）具有特异性，该蛋白在细菌和人类中高度保守。用体外灭活的结核分枝杆菌激活PBMC，然后用1)灭活的结核分枝杆菌和2)完整的重组65-kDa牛分枝杆菌/M热休克蛋白（hsp）对自体靶细胞进行CTL活性检测。肺结核;或3)重组65-kDa hsp的色氨酸片段。用杀死的结核分枝杆菌或65-kDa热休克蛋白的胰蛋白酶片段引物的靶细胞CTL活性较强，而用完整的65-kDa热休克蛋白引物的靶细胞CTL活性较弱。结核杆菌激活的T细胞来自2/13的供体，对未启动的目标发挥杀伤活性。为了评估T细胞反应是否针对分枝杆菌和人类65-kDa热休克蛋白共有的自身表位，合成了四个至少10个氨基酸长度的肽，对应于这些分子的完全或几乎相同的区域。来自8/9个个体的外周血T细胞在被杀死的结核分枝杆菌激活后，对由一种或多种这些合成肽引物的自体靶标表达了很强的CTL活性。通过使用转染HLA-DR的小鼠L细胞，我们发现这些表位在组织相容性HLA-DR （II类）分子的背景下被识别。我们的结论是，T细胞在体外对自身表位具有特异性并不表明自身免疫性疾病。然而，如果在感染的某些阶段，这些T细胞被交叉反应性微生物表位激活，它们可能引起自身免疫反应。
The immune response to mycobacterial pathogens comprises a significant percentage of T cells with specificity for a 65-kDa heat shock protein (hsp) which is highly conserved in bacteria and man. PBMC were activated in vitro with killed Mycobacterium tuberculosis and afterward tested for CTL activity on autologous target cells primed with 1) killed M. tuberculosis, 2) intact recombinant 65-kDa hsp of Mycobacterium bovis/M. tuberculosis; or 3) tryptic fragments of the recombinant 65-kDa hsp. Strong CTL activity was observed on targets primed with killed M. tuberculosis or with tryptic fragments of the 65-kDa hsp, but not on those primed with the intact 65-kDa hsp. M. tuberculosis activated T cells from 2/13 donors tested exerted killer activity against unprimed targets. To assess whether T cell responses were directed against self-epitopes shared by the mycobacterial and human 65-kDa hsp, four peptides of at least 10 amino acids length were synthesized corresponding to fully or almost identical regions of these molecules. Peripheral blood T cells from 8/9 individuals tested, after activation with killed M. tuberculosis, expressed strong CTL activity toward autologous targets primed with one or more of these synthetic peptides. By using HLA-DR transfected murine L cells we found that the epitopes were recognized in the context of histocompatible HLA-DR (class II) molecules. We conclude that the demonstration of T cells with specificity to self-epitopes in vitro is not indicative for autoimmune disease. However, if at certain stages of infection such T cells are activated by crossreactive microbial epitopes they could cause autoimmune responses.