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.

Keywords: MTB; CD4+ T-cell epitope; IFN-γ; Proliferation; active TB patient; class II restriction.