T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection

Nat Med. 2023 Jan;29(1):258-269. doi: 10.1038/s41591-022-02110-9. Epub 2023 Jan 5.

Abstract

Antigen-specific, MHC-restricted αβ T cells are necessary for protective immunity against Mycobacterium tuberculosis, but the ability to broadly study these responses has been limited. In the present study, we used single-cell and bulk T cell receptor (TCR) sequencing and the GLIPH2 algorithm to analyze M. tuberculosis-specific sequences in two longitudinal cohorts, comprising 166 individuals with M. tuberculosis infection who progressed to either tuberculosis (n = 48) or controlled infection (n = 118). We found 24 T cell groups with similar TCR-β sequences, predicted by GLIPH2 to have common TCR specificities, which were associated with control of infection (n = 17), and others that were associated with progression to disease (n = 7). Using a genome-wide M. tuberculosis antigen screen, we identified peptides targeted by T cell similarity groups enriched either in controllers or in progressors. We propose that antigens recognized by T cell similarity groups associated with control of infection can be considered as high-priority targets for future vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens
  • Disease Progression
  • Humans
  • Mycobacterium tuberculosis*
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocytes
  • Tuberculosis* / genetics

Substances

  • Receptors, Antigen, T-Cell
  • Antigens