T Cells Specific for a Mycobacterial Glycolipid Expand after Intravenous Bacillus Calmette-Guérin Vaccination

J Immunol. 2021 Mar 15;206(6):1240-1250. doi: 10.4049/jimmunol.2001065. Epub 2021 Feb 3.


Intradermal vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) protects infants from disseminated tuberculosis, and i.v. BCG protects nonhuman primates (NHP) against pulmonary and extrapulmonary tuberculosis. In humans and NHP, protection is thought to be mediated by T cells, which typically recognize bacterial peptide Ags bound to MHC proteins. However, during vertebrate evolution, T cells acquired the capacity to recognize lipid Ags bound to CD1a, CD1b, and CD1c proteins expressed on APCs. It is unknown whether BCG induces T cell immunity to mycobacterial lipids and whether CD1-restricted T cells are resident in the lung. In this study, we developed and validated Macaca mulatta (Mamu) CD1b and CD1c tetramers to probe ex vivo phenotypes and functions of T cells specific for glucose monomycolate (GMM), an immunodominant mycobacterial lipid Ag. We discovered that CD1b and CD1c present GMM to T cells in both humans and NHP. We show that GMM-specific T cells are expanded in rhesus macaque blood 4 wk after i.v. BCG, which has been shown to protect NHP with near-sterilizing efficacy upon M. tuberculosis challenge. After vaccination, these T cells are detected at high frequency within bronchoalveolar fluid and express CD69 and CD103, markers associated with resident memory T cells. Thus, our data expand the repertoire of T cells known to be induced by whole cell mycobacterial vaccines, such as BCG, and show that lipid Ag-specific T cells are resident in the lungs, where they may contribute to protective immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / metabolism
  • Antigens, CD1 / metabolism
  • BCG Vaccine / administration & dosage*
  • Cell Line
  • Child
  • Cohort Studies
  • Disease Models, Animal
  • Female
  • Glycolipids / immunology*
  • Glycoproteins / metabolism
  • Healthy Volunteers
  • Humans
  • Injections, Intravenous
  • Lung / cytology
  • Lung / immunology
  • Lung / microbiology
  • Macaca mulatta
  • Male
  • Mycobacterium bovis / immunology
  • Mycobacterium tuberculosis / immunology
  • Primary Cell Culture
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tuberculosis / blood
  • Tuberculosis / immunology
  • Tuberculosis / microbiology
  • Tuberculosis / prevention & control*


  • Antigens, Bacterial
  • Antigens, CD1
  • BCG Vaccine
  • CD1C protein, human
  • CD1b antigen
  • Glycolipids
  • Glycoproteins