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.
Keywords:
MTB; CD4+ T-cell epitope; IFN-γ; Proliferation; active TB patient; class II restriction.
© 2016 Federation of European Biochemical Societies.
MeSH terms
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Alleles
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Amino Acid Sequence
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Antigens, Bacterial / chemistry
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Antigens, Bacterial / immunology*
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Biological Assay
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / immunology
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Cell Proliferation
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Epitopes, T-Lymphocyte / chemistry
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Epitopes, T-Lymphocyte / immunology*
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Gene Expression
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Gene Frequency
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HLA-DRB1 Chains / genetics
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HLA-DRB1 Chains / immunology*
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Humans
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Interferon-alpha / biosynthesis
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Interferon-alpha / metabolism
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Interferon-gamma / biosynthesis
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Interferon-gamma / metabolism
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Interleukin-17 / biosynthesis
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Interleukin-17 / metabolism
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Interleukin-4 / biosynthesis
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Interleukin-4 / metabolism
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Mycobacterium tuberculosis / chemistry
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Mycobacterium tuberculosis / growth & development
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Mycobacterium tuberculosis / immunology*
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Peptides / chemical synthesis
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Peptides / pharmacology*
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Primary Cell Culture
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Tuberculosis, Pulmonary / immunology*
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Tuberculosis, Pulmonary / microbiology
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antigens, Bacterial
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Epitopes, T-Lymphocyte
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HLA-DRB1 Chains
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HLA-DRB1*09:01 antigen
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IL4 protein, human
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Interferon-alpha
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Interleukin-17
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Peptides
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Tumor Necrosis Factor-alpha
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Interleukin-4
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Interferon-gamma
Associated data
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GENBANK/NP_218321.1
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GENBANK/YP_177770.1