title: Identification of HLA-DRB1*09:01-restricted Mycobacterium tuberculosis CD4+T-cell epitopes.
abstract: CD4+T cells play an essential role in protection against Mycobacterium tuberculosis (MTB) infection. We identified three HLA-DRB1*09:01-restricted CD4+T-cell epitopes derived from the dominant secreted MTB antigens 38 kDa (Rv3804c) and Ag85A (Rv0934). The antigens were screened for epitopes by in silico prediction programs and analysis of IFN-γ induction in the peripheral blood mononuclear cells (PBMCs) from TB patients. In response to three of the high-affinity predicted epitopes derived from 38 kDa and Ag85A, CD4+T cells from HLA-DRB1*09:01 TB patients were stimulated to produce IFN-γ and Tumor Necrosis Factor (TNF)-α. The three epitopes were also found to induce the proliferation of CD4+T cells by carboxyfluorescein succinimidyl ester-diluted assays. These HLA-DRB1*09:01-restricted CD4+T-cell epitopes facilitate analysis of the role of 38 kDa- and Ag85A-specific T cells in MTB infection and pave way for the design of vaccines against tuberculosis.
authors.affiliation: Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Su-Dong
authors.initials: SD
authors.lastname: Liu
authors.affiliation: Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Shi-Meng
authors.initials: SM
authors.lastname: Zhang
authors.affiliation: Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Jian-Chun
authors.initials: JC
authors.lastname: He
authors.affiliation: Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Xia-Lin
authors.initials: XL
authors.lastname: Du
authors.affiliation: Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001681:Biological Assay; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015870:Gene Expression; D005787:Gene Frequency; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000254:growth & development / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D061251:Primary Cell Culture; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; C487381:HLA-DRB1*09:01 antigen; C508598:IL4 protein, human; D016898:Interferon-alpha; D020381:Interleukin-17; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: 
  MTB
  ; CD4+ T-cell epitope; IFN-γ; Proliferation; active TB patient; class II restriction