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Title: | T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection |
Authors: | Musvosvi, M Huang, H Wang, C Xia, Q Rozot, V Krishnan, A Acs, P Cheruku, A Obermoser, G Leslie, A Behar, SM Hanekom, WA Bilek, N Fisher, M Kaufmann, SHE Walzl, G Hatherill, M Davis, MM Scriba, TJ Kafaar, F Workman, L Mulenga, H Hughes, EJ Erasmus, M Nombida, O Veldsman, A Cloete, Y Abrahams, D Moyo, S Gelderbloem, S Tameris, M Geldenhuys, H Hussey, G Ehrlich, R Verver, S Geiter, L Black, GF van der Spuy, G Stanley, K Kriel, M Du Plessis, N Nene, N Roberts, T Kleynhans, L Gutschmidt, A Smith, B Loxton, AG Chegou, NN Tromp, G Tabb, D Ottenhoff, THM Klein, MR Haks, MC Franken, KLMC Geluk, A van Meijgaarden, KE Joosten, SA Boom, WH Thiel, B Mayanja-Kizza, H Joloba, M Zalwango, S Nsereko, M Okwera, B Kisingo, H Parida, SK Golinski, R Maertzdorf, J Weiner, J Jacobson, M Dockrell, HM Lalor, M Smith, S Gorak-Stolinska, P Hur, YG Lee, JS Crampin, AC French, N Ngwira, B Ben-Smith, A Watkins, K Ambrose, L Simukonda, F Mvula, H Chilongo, F Saul, J Branson, K Suliman, S Mahomed, H |
Keywords: | immunological surveillance;infection;T-cell receptor;tuberculosis |
Issue Date: | 5-Jan-2023 |
Publisher: | Nature Research (part of Springer Nature) |
Citation: | Musvosvi, M. et al. for the Adolescent Cohort Study team & GC6-74 Consortium (2023) 'T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection', Nature Medicine, 29 (1), pp. 258 - 269. doi: 10.1038/s41591-022-02110-9. |
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. |
Description: | Data availability: The datasets and scripts to generate the manuscript figures are available at https://github.com/SATVILab/DataTidyMusvosviTCRseq. The raw bulk CDR3α and CDR3β sequence data from the ACS and GC6-74 participants are available at https://doi.org/10.21417/MM2022NM. Online content: Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at https://doi.org/10.1038/s41591-022-02110-9. |
URI: | http://bura.brunel.ac.uk/handle/2438/29277 |
DOI: | http://dx.doi.org/10.1038/s41591-022-02110-9 |
ISSN: | 1078-8956 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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