Host immune responses to antigens derived from a predominant strain of Mycobacterium tuberculosis

Abstract

OBJECTIVES: Beijing strain of Mycobacterium tuberculosis (M. tb) is characterized by a high incidence of transmission, relapse, and drug resistance. This study aimed to determine host immune responses to antigens derived from the Beijing/K strain which has been highly prevalent in tuberculosis (TB) outbreaks in South Korea. METHODS: We recruited 52 TB patients and 96 healthy subjects comprising 31 individuals with latent TB infection (LTBI) and 65 TB-naive controls based on QuantiFERON-TB Gold In-Tube (QFT-IT) tests. Blood samples were obtained for diluted whole-blood assays, multiplex bead arrays, ELISpot assays, and HLA typing. Molecular genotyping of M. tb was performed using clinical isolates. RESULTS: Active TB and LTBI groups were differentiated by TNF-alpha concentrations induced by the Beijing/K strain-derived antigens, MTBK_24790 and MTBK_24800 (P < 0.001). MTBK_24800-induced IFN-gamma and CXCL10 concentrations discriminated the TB-infected groups from TB-naive controls (P < 0.001). IFN-gamma-producing T cells were generated in 87.2% of TB patients in response to MTBK_24800 peptide antigens. The major immunogenic epitope was at C-terminal of the antigen, and predominantly recognized by HLA-DR4 and -DQ4. CONCLUSIONS: Measurement of IFN-gamma, CXCL10, and TNF-alpha concentrations induced by MTBK_24790 and MTBK_24800 may contribute to improved diagnosis of TB and vaccine development in regions where the Beijing/K strain is endemic.