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

J Infect. 2016 Jul;73(1):54-62. doi: 10.1016/j.jinf.2016.04.032. Epub 2016 May 4.

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-naïve 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-α concentrations induced by the Beijing/K strain-derived antigens, MTBK_24790 and MTBK_24800 (P < 0.001). MTBK_24800-induced IFN-γ and CXCL10 concentrations discriminated the TB-infected groups from TB-naïve controls (P < 0.001). IFN-γ-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-γ, CXCL10, and TNF-α 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.

Keywords: Beijing/K strain; CXCL10; IFN-γ; Latent TB infection; Mycobacterium tuberculosis; TB; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Bacterial / immunology*
  • Cytokines / analysis
  • Disease Outbreaks
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Republic of Korea / epidemiology
  • Tuberculosis / diagnosis
  • Tuberculosis / epidemiology
  • Tuberculosis / microbiology*
  • Young Adult

Substances

  • Antigens, Bacterial
  • Cytokines
  • Epitopes, T-Lymphocyte