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

作者：Munyaradzi Musvosvi, Huang Huang, Chunlin Wang, Qiong Xia, Virginie Rozot, Akshaya Krishnan, Péter Ács, Abhilasha Cheruku, Gerlinde Obermoser, Alasdair J. Leslie, Samuel M. Behar, Willem A. Hanekom, Nicole Bilek, Michelle L. 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 Ann Abrahams, Sizulu Moyo, Sebastian Gelderbloem, Michele D. Tameris, Hennie D. Geldenhuys, Willem Albert Hanekom, Gregory Dudley Hussey, Rodney I Ehrlich, Suzanne Verver, Larry Geiter, Gerhard Walzl, Gillian F. Black, Gian D van der Spuy, Kim Stanley, Magdalena Kriel, Nelita du Plessis, Nonhlanhla Nene, Teri Roberts, Léanie Kleynhans, Andrea Gutschmidt, Bronwyn Smith, Andre Gareth 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 Lutaakome Joloba, Sarah K Zalwango, Mary Nsereko, Brenda Okwera, Hussein Kisingo, Stefan H. E. Kaufmann, (GC6-74 principal investigator), Shreemanta K. Parida, Robert Golinski, Jeroen Maertzdorf, January Mikolaj Weiner, Mark Z. Jacobson, Hazel M. Dockrell, Maeve K. Lalor, Steven G. Smith, Patricia Gorak‐Stolinska, Yun‐Gyoung Hur, Ji‐Sook Lee, Amelia Catharine Crampin, Neil French, Bagrey M. Ngwira, Anne Ben‐Smith, Kate E. Watkins, Lyn R. Ambrose, Felanji Simukonda, Hazzie Mvula, Femia Chilongo, Jacky Saul, Keith R. Branson, Sara Suliman, Thomas J. Scriba, Hassan Mahomed, E. Jane Hughes, Nicole Bilek, Mzwandile Erasmus, Onke Nombida, Ashley Veldsman, Katrina J. Downing, Michelle L. Fisher, Adam Penn‐Nicholson, Humphrey Mulenga, Brian Abel, Mark Bowmaker, Benjamin M. N. Kagina, William Kwong Chung, Willem A. Hanekom, Jerry Sadoff, Donata R. Sizemore, Srinivasan Ramachandran, Lew Barker, Michael J. Brennan, Frank Weichold, Stefanie Müller, Larry Geiter, Desta Kassa, Almaz Abebe, Tsehayenesh Mesele, Belete Tegbaru, Debbie van Baarle, Frank Miedema, Rawleigh Craig Howe, Adane Mihret, Abraham Aseffa, Yonas Bekele, Rachel Iwnetu, Mesfin Tafesse, Lawrence K Yamuah, Martin O. C. Ota, Jayne S. Sutherland, Philip C. Hill, Richard Adebayo Adegbola, Tumani Corrah, Martín Antonio, Toyin Omotayo Togun, Ifedayo Adetifa, Simon A. Donkor, Peter Lawætz Andersen, Ida Rosenkrands, Mark T. Doherty, Karin Nana Weldingh, Gary K. Schoolnik, Gregory Dolganov, Trần Thị Thanh Vân · 发表于：Nature Medicine · 年份：2023 · DOI：10.1038/s41591-022-02110-9 · 被引用次数：107 · 研究领域：Tuberculosis Research and Epidemiology、Mycobacterium research and diagnosis、Infectious Diseases and Tuberculosis

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.