MHC class II tetramer guided detection of Mycobacterium tuberculosis-specific CD4+ T cells in peripheral blood from patients with pulmonary tuberculosis

Scand J Immunol. 2007 May;65(5):467-78. doi: 10.1111/j.1365-3083.2007.01924.x.


Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition to the more than 100-year-old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4 tetrameric complexes to visualize ex vivo CD4(+) T cells directed against the antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and other Mycobacterium species, and CD4(+) T cells which recognize the MTB-associated ESAT-6 antigen. MTB-reactive CD4(+) T cells reside predominantly in the CD45RA(+) CD28(+) and CD45(-) CD28(+) T-cell subset and recognize naturally processed and presented MTB epitopes. HLA-DR4-restricted, Ag85B or ESAT-6-specific CD4(+) T cells show similar dynamics over time in peripheral blood mononuclear cells (PBMC) when compared with CD8(+) T cells directed against the corresponding HLA-A2-presented MTB epitopes in patients with pulmonary MTB infection and subsequent successful therapy. This was not found to be true for T-cell responses directed against the 19-kDa lipoprotein. The dissection of the cellular immune response in M. tuberculosis infection will enable novel strategies for monitoring MTB vaccine candidates and to gauge CD4(+) T cells directed against MTB.

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / microbiology*
  • Epitopes, T-Lymphocyte / blood*
  • Histocompatibility Antigens Class II / blood*
  • Histocompatibility Antigens Class II / chemistry
  • Humans
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / pathology


  • Antigens, Bacterial
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II