Immune response to Mycobacterium tuberculosis specific antigen ESAT-6 among south Indians

Immune response to Mycobacterium tuberculosis specific antigen ESAT-6 among south Indians
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DOI:
10.1016/j.tube.2009.10.003
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发表时间:
2010-01-01
期刊:
影响因子:
3.2
通讯作者:
Raja, Alamelu
Raja, Alamelu
中科院分区:
医学4区
文献类型:
--
作者:
Kumar, Madhan;Meenakshi, N.;Raja, Alamelu

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6 kDa早期分泌抗原靶标(ESAT-6)是一种被结核分枝杆菌感染者识别的T细胞抗原。这项研究的目的是在南印度人群中确定ESAT-6蛋白的“保护性表位”。用流式细胞术和酶联免疫吸附试验(ELISA)检测ESAT-6多肽对细胞增殖和干扰素-γ(IFN-γ)的影响。健康家庭接触者(HHC)识别ESP1(10/17)和ESP6(9/17)肽。肺结核患者中以ESP1(3/11)和ESP6(5/11)为主。治疗组ESP1、ESP8最大反应(7/10)。应答者的中位数结果如下:ESP1(76 pg/ml)、ESP6(pg/ml)能诱导HHC产生干扰素-g,PTB对这些多肽的反应较低。对ESP1(141pg/ml)、ESP8(102pg/ml)有反应。所有多肽在PTB和TR中对CD4细胞的增殖作用相似,但HHC显示ESP1(p<0.05)和Esp6(p<0.01)的增殖增加。ESP1(氨基酸AA1-20)和ESP6(AA51-70)是HHC中等位基因HLADRB1*04和HLADRB1*10识别的免疫原肽。但等位基因与ESAT-6肽呈递之间的关联需要在大量受试者中得到证实。我们推测ESAT-6可以与其他免疫诱导蛋白一起用于南印度人群的疫苗设计策略。(C)2009爱思唯尔有限公司。保留所有权利。
The 6-kDa early secreted antigenic target (ESAT-6) is a T-cell antigen recognized by individuals infected with Mycobacterium tuberculosis. The aim of the study was to identify "protective epitopes'' of ESAT-6 protein in the south Indian population. Proliferative and Interferon gamma (IFN-gamma) responses to ESAT-6 peptides were studied by flow cytometry and Enzyme linked immunosorbent assay (ELISA). Healthy household contacts (HHC) recognized Esp1 (10/17) and Esp6 (9/17) peptides. Among pulmonary tuberculosis patients (PTB), Esp1 (3/11) and Esp6 (5/11) were recognized. Maximal response (7/10) was found for Esp1 and Esp8 in treated patients (TR). Median values for the responding subjects gave the following results: Esp1 (76 pg/ml), Esp6 (64 pg/ml), induced IFN-g production in HHC; PTB gave low IFN-g responses for the peptides. TR responded to the peptides Esp1 (141 pg/ml), Esp8 (102 pg/ml). The proliferation of CD4 cells was similar in both PTB and TR for all peptides; but HHC showed an increase for Esp1 (p < 0.05) and Esp6 (p < 0.01). Esp1 (amino acids aa 1-20) and Esp6 (aa 51-70) were the immunogenic peptides recognized by the alleles HLA DRB1*04 and HLA DRB1*10 among HHC. But the association of the alleles with ESAT-6 peptide presentation needs to be confirmed in a large cohort of subjects. We speculate that ESAT-6 can be used along with other immune-eliciting proteins for vaccine design strategies in south Indian population. (C) 2009 Elsevier Ltd. All rights reserved.