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

Musvosvi, M.; Huang, H.; Wang, C.L.; Xia, Q.; Rozot, V.; Krishnan, A.; Acs, P.; Cheruku, A.; Obermoser, G.; Leslie, A.; Behar, S.M.; Hanekom, W.A.; Bilek, N.; Fisher, M.; Kaufmann, S.H.E.; Walzl, G.; Hatherill, M.; Davis, M.M.; Scriba, T.J.; Adolescent Cohort Study Team; GC6-74 Consortium

doi:doi:10.1038/s41591-022-02110-9

Antigen-specific, MHC-restricted alpha l3 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-beta 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...Show moreAntigen-specific, MHC-restricted alpha l3 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-beta 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.Show less

Leiden University Scholarly Publications

View statistics

Documents

In Collections

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