Hussain R, Dockrell H M, Shahid F, Zafar S, Chiang T J
Department of Microbiology, The Aga Khan University, Karachi, Pakistan.
Clin Exp Immunol. 1998 Nov;114(2):204-9. doi: 10.1046/j.1365-2249.1998.00708.x.
T cell responses play a critical role in determining protective responses to leprosy. Patients with self-limiting tuberculoid leprosy show high T cell reactivity, while patients with disseminated lepromatous form of the disease show absent to low levels of T cell reactivity. Since the T cell reactivity of lepromatous patients to purified protein derivative (PPD), a highly cross-reactive antigen, is similar to that of tuberculoid patients, we queried if lepromatous patients could recognize cross-reactive epitopes in Mycobacterium leprae antigens as well. T cell responses were analysed to a recombinant antigen 10-kD (a heat shock cognate protein) which is available from both M. tuberculosis (MT) and M. leprae (ML) and displays 90% identity in its amino acid sequence. Lymphoproliferative responses were assessed to ML and MT 10 kD in newly diagnosed leprosy patients (lepromatous, n = 23; tuberculoid, n = 65). Lepromatous patients showed similar, but low, lymphoproliferative responses to ML and MT 10 kD, while tuberculoid patients showed much higher responses to ML 10 kD. This suggests that the tuberculoid patients may be recognizing both species-specific and cross-reactive epitopes in ML 10 kD, while lepromatous patients may be recognizing only cross-reactive epitopes. This was further supported by linear regression analysis. Lepromatous patients showed a high concordance in T cell responses between ML and MT 10 kD (r=0.658; P<0.0006) not observed in tuberculoid patients (r=0.203; P>0.1). Identification of cross-reactive T cell epitopes in M. leprae which could induce protective responses should prove valuable in designing second generation peptide-based vaccines.
T细胞反应在决定麻风病的保护性反应中起关键作用。具有自限性结核样型麻风病的患者表现出高T细胞反应性，而患有播散性瘤型麻风病的患者则表现出缺乏或低水平的T细胞反应性。由于瘤型麻风病患者对纯化蛋白衍生物（PPD，一种高度交叉反应性抗原）的T细胞反应性与结核样型患者相似，我们质疑瘤型麻风病患者是否也能识别麻风分枝杆菌抗原中的交叉反应性表位。对一种重组抗原10-kD（一种热休克同源蛋白）进行了T细胞反应分析，该抗原可从结核分枝杆菌（MT）和麻风分枝杆菌（ML）中获得，其氨基酸序列具有90%的同一性。对新诊断的麻风病患者（瘤型，n = 23；结核样型，n = 65）的ML和MT 10 kD进行了淋巴细胞增殖反应评估。瘤型麻风病患者对ML和MT 10 kD表现出相似但较低的淋巴细胞增殖反应，而结核样型患者对ML 10 kD的反应则高得多。这表明结核样型患者可能识别ML 10 kD中的物种特异性和交叉反应性表位，而瘤型麻风病患者可能只识别交叉反应性表位。线性回归分析进一步支持了这一点。瘤型麻风病患者在ML和MT 10 kD之间的T细胞反应中表现出高度一致性（r = 0.658；P < 0.0006），而结核样型患者未观察到这种一致性（r = 0.203；P > 0.1）。鉴定麻风分枝杆菌中可诱导保护性反应的交叉反应性T细胞表位在设计基于肽的第二代疫苗方面应具有重要价值。
