T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection
Authors: Musvosvi Munyaradzi , Huang Huang , Wang Chunlin , Xia Qiong , Rozot Virginie , Krishnan Akshaya , Acs Peter , Cheruku Abhilasha , Obermoser Gerlinde , Leslie Alasdair , Behar Samuel M. , Hanekom Willem A. , Bilek Nicole , Fisher Michelle , Kaufmann Stefan H. E. , Walzl Gerhard , Hatherill Mark , Davis Mark M. , Scriba Thomas J. ,   Adolescent Cohort Study team, Kafaar Fazlin , Workman Leslie , Mulenga Humphrey , Scriba Thomas J. , Hughes E. Jane , Bilek Nicole , Erasmus Mzwandile , Nombida Onke , Veldsman Ashley , Cloete Yolundi , Abrahams Deborah , Moyo Sizulu , Gelderbloem Sebastian , Tameris Michele , Geldenhuys Hennie , Hanekom Willem , Hussey Gregory , Ehrlich Rodney , Verver Suzanne , Geiter Larry ,   GC6-74 Consortium, Walzl Gerhard , Black Gillian F. , van der Spuy Gian , Stanley Kim , Kriel Magdalena , Du Plessis Nelita , Nene Nonhlanhla , Roberts Teri , Kleynhans Leanie , Gutschmidt Andrea , Smith Bronwyn , Loxton Andre G. , Chegou Novel N. , Tromp Gerhardus , Tabb David , Ottenhoff Tom H. M. , Klein Michel R. , Haks Marielle C. , Franken Kees L. M. C. , Geluk Annemieke , van Meijgaarden Krista E. , Joosten Simone A. , Boom W. Henry , Thiel Bonnie , Mayanja-Kizza Harriet , Joloba Moses , Zalwango Sarah , Nsereko Mary , Okwera Brenda , Kisingo Hussein , Kaufmann Stefan H. E. ,   (GC6-74 principal investigator), Parida Shreemanta K. , Golinski Robert , Maertzdorf Jeroen , Weiner January , Jacobson Marc , Dockrell Hazel M. , Lalor Maeve , Smith Steven , Gorak-Stolinska Patricia , Hur Yun-Gyoung , Lee Ji-Sook , Crampin Amelia C. , French Neil , Ngwira Bagrey , Ben-Smith Anne , Watkins Kate , Ambrose Lyn , Simukonda Felanji , Mvula Hazzie , Chilongo Femia , Saul Jacky , Branson Keith , Suliman Sara , Scriba Thomas J. , Mahomed Hassan , Hughes E. Jane , Bilek Nicole , Erasmus Mzwandile , Nombida Onke , Veldsman Ashley , Downing Katrina , Fisher Michelle , Penn-Nicholson Adam , Mulenga Humphrey , Abel Brian , Bowmaker Mark , Kagina Benjamin , Chung William Kwong , Hanekom Willem A. , Sadoff Jerry , Sizemore Donata , Ramachandran S. , Barker Lew , Brennan Michael , Weichold Frank , Muller Stefanie , Geiter Larry , Kassa Desta , Abebe Almaz , Mesele Tsehayenesh , Tegbaru Belete , van Baarle Debbie , Miedema Frank , Howe Rawleigh , Mihret Adane , Aseffa Abraham , Bekele Yonas , Iwnetu Rachel , Tafesse Mesfin , Yamuah Lawrence , Ota Martin , Sutherland Jayne , Hill Philip , Adegbola Richard , Corrah Tumani , Antonio Martin , Togun Toyin , Adetifa Ifedayo , Donkor Simon , Andersen Peter , Rosenkrands Ida , Doherty Mark , Weldingh Karin , Schoolnik Gary , Dolganov Gregory , Van Tran 
Published: January 2023

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.