Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis

Genes Immun. 2007 Jun;8(4):334-43. doi: 10.1038/sj.gene.6364392. Epub 2007 Apr 12.


Challenged by scattered understanding of protective immunity to Mycobacterium tuberculosis (MTB), we have mapped peptide epitopes to human leukocyte antigen (HLA)-A*0101, A*0201, A*1101, A*2402, B*0702, B*0801 and B*1501 of the secreted mycobacterial antigen Ag85B, a vaccine candidate that may be associated with immune protection. Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis for individual peptide species on HLA-A and HLA-B molecules revealed binding ranges between 10(-3) and 10(-7) M. After selection of the best matches, major histocompatibility complex class I/peptide tetramer complexes were constructed to measure the CD8+ T-cell responses directly ex vivo in peripheral blood mononuclear cells (PBMC) derived from 57 patients with acute pulmonary tuberculosis. Three patterns of (allele-) specific CD8+ recognition were identified: (a). Focus on one dominant epitope with additional recognition of several subdominant T-cell epitopes (HLA-A*0301, A*2402, B*0801 and B*1501); (b). Co-dominant recognition of two distinct groups of peptides presented by HLA-B*0702; and (c). Diverse and broad recognition of peptides presented by HLA-A*0201. Peptides that bound with slow off-rates to class I alleles, that is HLA-A*0201, were associated with low frequency of CD8+ T cells in PBMCs from patients with tuberculosis. HLA-B alleles showed fast off-rates in peptide binding and restricted high numbers (up to 6%) of antigen-specific CD8+ T cells in patients with pulmonary tuberculosis.

MeSH terms

  • Alleles
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Epitope Mapping*
  • Flow Cytometry
  • Genes, MHC Class I*
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology
  • Humans
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis, Pulmonary / genetics*
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / physiopathology


  • HLA-A Antigens
  • HLA-B Antigens