T Cell Receptor Repertoires Associated with Control and Disease Progression following Mycobacterium Tuberculosis Infection

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.
T cell receptor, Mycobacterium, tuberculosis infection
Musvosvi, M., Huang, H., Wang, C., Xia, Q., Rozot, V., Krishnan, A., ... & Van, T. (2023). T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection. Nature Medicine, 1-12.https://doi.org/10.1038/s41591-022-02110-9