T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection
Munyaradzi Musvosvi, Huang Huang, Chunlin Wang, Qiong Xia, Virginie Rozot, Akshaya Krishnan, Péter Ács, Abhilasha Cheruku, Gerlinde Obermoser, Alasdair Leslie, Samuel M. Behar, Willem A. Hanekom, Nicole Bilek, Michelle Fisher, Stefan H. E. Kaufmann, Gerhard Walzl, Mark Hatherill, Mark M. Davis, Thomas J. Scriba, Adolescent Cohort Study team, Fazlin Kafaar, Leslie Workman, Humphrey Mulenga, Thomas J. Scriba, E. Jane Hughes, Nicole Bilek, Mzwandile Erasmus, Onke Nombida, Ashley Veldsman, Yolundi Cloete, Deborah Abrahams, Sizulu Moyo, Sebastian Gelderbloem, Michèle Tameris, Hennie Geldenhuys, Willem A. Hanekom, Gregory Hussey, Rodney Ehrlich, Suzanne Verver, Larry Geiter, Gerhard Walzl, Gillian F. Black, Gian van der Spuy, Kim Stanley, Magdalena Kriel, Nelita du Plessis, Nonhlanhla Nene, Teri Roberts, Léanie Kleynhans, Andrea Gutschmidt, Bronwyn Smith, André G. Loxton, Novel N. Chegou, Gerhardus Tromp, David L. Tabb, Tom H. M. Ottenhoff, Michèl R. Klein, Mariëlle C. Haks, Kees L. M. C. Franken, Annemieke Geluk, Krista E. van Meijgaarden, Simone A. Joosten, W. Henry Boom, Bonnie Thiel, Harriet Mayanja‐Kizza, Moses Joloba, Sarah Zalwango, Mary Nsereko, Brenda Okwera, Hussein Kisingo, Stefan H. E. Kaufmann, (GC6-74 principal investigator), Shreemanta K. Parida, Robert Golinski, Jeroen Maertzdorf, January Weiner, Mark Z. Jacobson, Hazel M. Dockrell, Maeve K. Lalor, Steven G. Smith, Patricia Gorak‐Stolinska, Yun‐Gyoung Hur, Ji‐Sook Lee, Amelia C. Crampin, Neil French, Bagrey Ngwira, Anne Ben‐Smith, Kate E. Watkins, Lyn Ambrose, Felanji Simukonda, Hazzie Mvula, Femia Chilongo, Jacky Saul, Keith Branson, Sara Suliman, Thomas J. Scriba, Hassan Mahomed, E. Jane Hughes, Nicole Bilek, Mzwandile Erasmus
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.