Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines

Eur J Immunol. 2015 Apr;45(4):1069-81. doi: 10.1002/eji.201445193. Epub 2015 Feb 17.


CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.

Keywords: CD8 T lymphocytes; HLA-E; Mycobacterium tuberculosis; TB; Tetramers; Type 2 cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / immunology
  • Cells, Cultured
  • Coinfection / immunology
  • Coinfection / microbiology
  • Coinfection / virology
  • Cytokines / biosynthesis*
  • Cytokines / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • HIV Infections / immunology
  • HIV Infections / virology
  • HLA-E Antigens
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • NK Cell Lectin-Like Receptor Subfamily C / immunology
  • NK Cell Lectin-Like Receptor Subfamily D / immunology
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Klrc2 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Antigen, T-Cell, alpha-beta