T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection
Publication date
2023-01
Authors
Musvosvi, Munyaradzi
Huang, Huang
Wang, Chunlin
Xia, Qiong
Rozot, Virginie
Krishnan, Akshaya
Acs, Peter
Cheruku, Abhilasha
Obermoser, Gerlinde
Leslie, Alasdair
Editors
Advisors
Supervisors
Document Type
Article
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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.
Keywords
General Biochemistry,Genetics and Molecular Biology
Citation
Musvosvi, M, Huang, H, Wang, C, 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, Kafaar, F, Workman, L, Mulenga, H, Scriba, T J, Hughes, E J, Bilek, N, Erasmus, M, Nombida, O, Veldsman, A, Cloete, Y, Abrahams, D, Moyo, S, Gelderbloem, S, Tameris, M, Geldenhuys, H, Hanekom, W, Hussey, G, Ehrlich, R, Verver, S, Geiter, L, Walzl, G, Black, G F, van der Spuy, G, Stanley, K, Kriel, M, Du Plessis, N, Nene, N, Roberts, T, Kleynhans, L, Gutschmidt, A, Smith, B, Loxton, A G, Chegou, N N, Tromp, G, Tabb, D, Ottenhoff, T H M, Klein, M R, Haks, M C, Franken, K L M C, Geluk, A, van Meijgaarden, K E, Joosten, S A, Boom, W H, Thiel, B, Mayanja-Kizza, H, Joloba, M, Zalwango, S, Nsereko, M, Okwera, B, Kisingo, H, Kaufmann, S H E, Parida, S K, Golinski, R, Maertzdorf, J, Weiner, J, Jacobson, M, Dockrell, H M, Lalor, M, Smith, S, Gorak-Stolinska, P, Hur, Y G, Lee, J S, Crampin, A C, French, N, Ngwira, B, Ben-Smith, A, Watkins, K, Ambrose, L, Simukonda, F, Mvula, H, Chilongo, F, Saul, J, Branson, K, Suliman, S, Scriba, T J, Mahomed, H, Hughes, E J, Bilek, N, Erasmus, M, Nombida, O, Veldsman, A, Downing, K, Fisher, M, Penn-Nicholson, A, Mulenga, H, Abel, B, Bowmaker, M, Kagina, B, Chung, W K, Hanekom, W A, Sadoff, J, Sizemore, D, Ramachandran, S, Barker, L, Brennan, M, Weichold, F, Muller, S, Geiter, L, Kassa, D, Abebe, A, Mesele, T, Tegbaru, B, van Baarle, D, Miedema, F, Howe, R, Mihret, A, Aseffa, A, Bekele, Y, Iwnetu, R, Tafesse, M, Yamuah, L, Ota, M, Sutherland, J, Hill, P, Adegbola, R, Corrah, T, Antonio, M, Togun, T, Adetifa, I, Donkor, S, Andersen, P, Rosenkrands, I, Doherty, M, Weldingh, K, Schoolnik, G, Dolganov, G & Van, T 2023, 'T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection', Nature medicine, vol. 29, no. 1, pp. 258-269. https://doi.org/10.1038/s41591-022-02110-9