ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Department of Medicine, Division of Infectious Diseases, University of Washington, Box 358061, Seattle, WA 98195, USA.
Tuberculosis (Edinb). 2015 May;95(3):275-87. doi: 10.1016/j.tube.2015.03.001. Epub 2015 Mar 27.
Elicitation of CD4 IFN-gamma T cell responses to Mycobacterium tuberculosis (MTB) is a rational vaccine strategy to prevent clinical tuberculosis. Diagnosis of MTB infection is based on T-cell immune memory to MTB antigens. The MTB proteome contains over four thousand open reading frames (ORFs). We conducted a pilot antigen identification study using 164 MTB proteins and MTB-specific T-cells expanded in vitro from 12 persons with latent MTB infection. Enrichment of MTB-reactive T-cells from PBMC used cell sorting or an alternate system compatible with limited resources. MTB proteins were used as single antigens or combinatorial matrices in proliferation and cytokine secretion readouts. Overall, our study found that 44 MTB proteins were antigenic, including 27 not previously characterized as CD4 T-cell antigens. Antigen truncation, peptide, NTM homology, and HLA class II tetramer studies confirmed malate synthase G (encoded by gene Rv1837) as a CD4 T-cell antigen. This simple, scalable system has potential utility for the identification of candidate MTB vaccine and biomarker antigens.
针对结核分枝杆菌（MTB）的 CD4 IFN-γ T 细胞反应的激发是预防临床结核病的合理疫苗策略。MTB 感染的诊断基于对 MTB 抗原的 T 细胞免疫记忆。MTB 蛋白质组包含超过 4000 个开放阅读框（ORFs）。我们使用来自 12 名潜伏性 MTB 感染者的体外扩增的 164 种 MTB 蛋白和 MTB 特异性 T 细胞进行了一项先导抗原鉴定研究。使用细胞分选或与有限资源兼容的替代系统从 PBMC 中富集 MTB 反应性 T 细胞。MTB 蛋白被用作增殖和细胞因子分泌检测的单一抗原或组合基质。总的来说，我们的研究发现 44 种 MTB 蛋白具有抗原性，其中包括 27 种以前未被表征为 CD4 T 细胞抗原的蛋白。抗原截断、肽、NTM 同源性和 HLA Ⅱ类四聚体研究证实了苹果酸合酶 G（由基因 Rv1837 编码）是一种 CD4 T 细胞抗原。这个简单、可扩展的系统具有鉴定候选 MTB 疫苗和生物标志物抗原的潜在用途。
