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印度南部人群对结核分枝杆菌特异性抗原 ESAT-6 的免疫应答。

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

机构信息

Department of Immunology, Tuberculosis Research Centre (ICMR), Mayor V. R. Ramanathan Road, Chetput, Chennai - 600 031, India.

出版信息

Tuberculosis (Edinb). 2010 Jan;90(1):60-9. doi: 10.1016/j.tube.2009.10.003. Epub 2009 Nov 27.

Abstract

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 (76pg/ml), Esp6 (64pg/ml), induced IFN-gamma production in HHC; PTB gave low IFN-gamma responses for the peptides. TR responded to the peptides Esp1 (141pg/ml), Esp8 (102pg/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 DRB104 and HLA DRB110 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.

摘要

6-kDa 早期分泌抗原靶标(ESAT-6)是一种被感染结核分枝杆菌的个体识别的 T 细胞抗原。本研究的目的是在印度南部人群中鉴定 ESAT-6 蛋白的“保护性表位”。通过流式细胞术和酶联免疫吸附试验(ELISA)研究 ESAT-6 肽的增殖和干扰素γ(IFN-γ)反应。健康的家庭接触者(HHC)识别 Esp1(10/17)和 Esp6(9/17)肽。在肺结核患者(PTB)中,Esp1(3/11)和 Esp6(5/11)被识别。在治疗患者(TR)中,Esp1 和 Esp8 的最大反应(7/10)被发现。反应性受试者的中位数值给出以下结果:Esp1(76pg/ml),Esp6(64pg/ml),在 HHC 中诱导 IFN-γ产生;PTB 对肽的 IFN-γ反应较低。TR 对肽 Esp1(141pg/ml),Esp8(102pg/ml)有反应。在所有肽段中,PTB 和 TR 的 CD4 细胞增殖相似;但是 HHC 对 Esp1(p<0.05)和 Esp6(p<0.01)表现出增加。Esp1(氨基酸 aa 1-20)和 Esp6(aa 51-70)是 HHC 中 HLA DRB104 和 HLA DRB110 等位基因识别的免疫原性肽段。但是,等位基因与 ESAT-6 肽呈递的关联需要在大量受试者队列中得到证实。我们推测 ESAT-6 可以与其他免疫激发蛋白一起用于印度南部人群的疫苗设计策略。

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