Adams E, Britton W, Morgan A, Sergeantson S, Basten A
Centenary Institute of Cancer Medicine and Cell Biology, Newtown NSW, Australia.
Scand J Immunol. 1994 Jun;39(6):588-96. doi: 10.1111/j.1365-3083.1994.tb03417.x.
The 70 kDa heat-shock protein (HSP) of Mycobacterium leprae stimulates both cellular and antibody responses in leprosy patients and subclinically infected individuals despite partial homology with host HSP70. Furthermore, mycobacterial HSP70 can act as a carrier protein in unprimed mice, suggesting the presence of widely shared T-cell determinants on this protein. In order to elucidate the frequency and genetic restriction of these T-cell epitopes, we have undertaken a systematic analysis of the proliferative responses to 20mer peptides encompassing the whole protein in different populations. Caucasian BCG vaccinees who responded to recombinant M. leprae HSP70 identified multiple scattered T-cell determinants, four of which were recognized by 60% of subjects in association with a variety of HLA-DR haplotypes. When a group of Nepali leprosy and tuberculosis patients were tested, significant differences in the pattern of peptide recognition were observed. The dominant peptides recognized by Caucasian subjects were infrequently reactive and other peptides were stimulatory, again in association with a variety of HLA-DR phenotypes. The C-terminal 70 residues of the M. leprae HSP70 are specific to M. leprae and sera from lepromatous leprosy patients bind to this region. However, few T-cell determinants were identified in these residues, indicating that this region is unhelpful as a diagnostic tool for detecting M. leprae-specific T-cell responses. When compared with the equivalent regions of the human HSP70, the commonly recognized peptides showed significant differences in amino-acid sequence. When taken in conjunction with the failure of human HSP70 to stimulate M. leprae HSP70-reactive T-cell clones (E. Adams et al., unpublished observations), this finding indicates that the human T-cell response to this protein is largely directed at mycobacterial-specific determinants. The presence of multiple T-cell epitopes on M. leprae HSP70 with varied patterns of HLA-DR association suggests that the whole protein is required for stimulating effective T-cell responses in genetically diverse populations.
尽管麻风分枝杆菌的70 kDa热休克蛋白（HSP）与宿主HSP70存在部分同源性，但它仍能刺激麻风患者和亚临床感染个体的细胞免疫和抗体反应。此外，分枝杆菌HSP70在未致敏小鼠中可作为载体蛋白，这表明该蛋白上存在广泛共享的T细胞决定簇。为了阐明这些T细胞表位的频率和遗传限制，我们对不同人群中针对覆盖整个蛋白的20聚体肽的增殖反应进行了系统分析。对白介素重组麻风分枝杆菌HSP70有反应的白种人卡介苗接种者识别出多个分散的T细胞决定簇，其中四个被60%的受试者识别，且与多种HLA - DR单倍型相关。当对一组尼泊尔麻风病和结核病患者进行检测时，观察到肽识别模式存在显著差异。白种人受试者识别的主要肽很少有反应性，而其他肽具有刺激作用，同样与多种HLA - DR表型相关。麻风分枝杆菌HSP70的C末端70个残基是麻风分枝杆菌特有的，瘤型麻风患者的血清可与该区域结合。然而，在这些残基中鉴定出的T细胞决定簇很少，这表明该区域作为检测麻风分枝杆菌特异性T细胞反应的诊断工具并无帮助。与人类HSP70的等效区域相比，常见识别的肽在氨基酸序列上存在显著差异。结合人类HSP70不能刺激麻风分枝杆菌HSP70反应性T细胞克隆这一现象（E. 亚当斯等人，未发表的观察结果），这一发现表明人类对该蛋白的T细胞反应主要针对分枝杆菌特异性决定簇。麻风分枝杆菌HSP70上存在多个T细胞表位，且与HLA - DR的关联模式各异，这表明在基因多样化的人群中，刺激有效的T细胞反应需要整个蛋白。
