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; Peter Acs; 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; 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; Michele Tameris; Hennie Geldenhuys; Willem 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; Leanie Kleynhans; Andrea Gutschmidt; Bronwyn Smith; Andre G. Loxton; Novel N. Chegou; Gerhardus Tromp; David Tabb; Tom H.M. Ottenhoff; Michel R. Klein; Marielle 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; Shreemanta K. Parida; Robert Golinski; Jeroen Maertzdorf; January Weiner; Marc Jacobson; Hazel M. Dockrell; Maeve Lalor; Steven Smith; Patricia Gorak-Stolinska; Yun Gyoung Hur; Ji Sook Lee; Amelia C. Crampin; Neil French; Bagrey Ngwira; Anne Ben-Smith; Kate 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; Onke Nombida; Ashley Veldsman; Katrina Downing; Michelle Fisher; Adam Penn-Nicholson; Humphrey Mulenga; Brian Abel; Mark Bowmaker; Benjamin Kagina; William Kwong Chung; Willem A. Hanekom; Jerry Sadoff; Donata Sizemore; S. Ramachandran; Lew Barker; Michael Brennan; Frank Weichold; Stefanie Muller; Larry Geiter; Desta Kassa; Almaz Abebe; Tsehayenesh Mesele; Belete Tegbaru; Debbie van Baarle; Frank Miedema; Rawleigh Howe; Adane Mihret; Abraham Aseffa; Yonas Bekele; Rachel Iwnetu; Mesfin Tafesse; Lawrence Yamuah; Martin Ota; Jayne Sutherland; Philip Hill; Richard Adegbola; Tumani Corrah; Martin Antonio; Toyin Togun; Ifedayo Adetifa; Simon Donkor; Peter Andersen; Ida Rosenkrands; Mark Doherty; Karin Weldingh; Gary Schoolnik; Gregory Dolganov; Tran Van

doi:10.1038/s41591-022-02110-9

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, Peter Acs, 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^*, Fazlin KafaarLeslie 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, Michele Tameris, Hennie Geldenhuys, Willem 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, Leanie Kleynhans, Andrea Gutschmidt, Bronwyn Smith, Andre G. Loxton, Novel N. Chegou, Gerhardus Tromp, David Tabb, Tom H.M. Ottenhoff, Michel R. Klein, Marielle 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, Shreemanta K. Parida, Robert Golinski, Jeroen Maertzdorf, January Weiner, Marc Jacobson, Hazel M. Dockrell, Maeve Lalor, Steven Smith, Patricia Gorak-Stolinska, Yun Gyoung Hur, Ji Sook Lee, Amelia C. Crampin, Neil French, Bagrey Ngwira, Anne Ben-Smith, Kate 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, Onke Nombida, Ashley Veldsman, Katrina Downing, Michelle Fisher, Adam Penn-Nicholson, Humphrey Mulenga, Brian Abel, Mark Bowmaker, Benjamin Kagina, William Kwong Chung, Willem A. Hanekom, Jerry Sadoff, Donata Sizemore, S. Ramachandran, Lew Barker, Michael Brennan, Frank Weichold, Stefanie Muller, Larry Geiter, Desta Kassa, Almaz Abebe, Tsehayenesh Mesele, Belete Tegbaru, Debbie van Baarle, Frank Miedema, Rawleigh Howe, Adane Mihret, Abraham Aseffa, Yonas Bekele, Rachel Iwnetu, Mesfin Tafesse, Lawrence Yamuah, Martin Ota, Jayne Sutherland, Philip Hill, Richard Adegbola, Tumani Corrah, Martin Antonio, Toyin Togun, Ifedayo Adetifa, Simon Donkor, Peter Andersen, Ida Rosenkrands, Mark Doherty, Karin Weldingh, Gary Schoolnik, Gregory Dolganov, Tran Van

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	258-269
Number of pages	12
Journal	Nature medicine
Volume	29
Issue number	1
DOIs	https://doi.org/10.1038/s41591-022-02110-9
Publication status	Published - Jan 2023

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s41591-022-02110-9Final published version, 8.79 MBLicence: CC BY

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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., ... Van, T. (2023). T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection. Nature medicine, 29(1), 258-269. https://doi.org/10.1038/s41591-022-02110-9

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title = "T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection",

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.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2023.",

year = "2023",

month = jan,

doi = "10.1038/s41591-022-02110-9",

language = "English",

volume = "29",

pages = "258--269",

journal = "Nature medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "1",

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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, Scriba, TJ, Hughes, EJ, 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, 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, Kaufmann, SHE, 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, Scriba, TJ, Mahomed, H, Hughes, EJ, Bilek, N, Erasmus, M, Nombida, O, Veldsman, A, Downing, K, Fisher, M, Penn-Nicholson, A, Mulenga, H, Abel, B, Bowmaker, M, Kagina, B, Chung, WK, Hanekom, WA, 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

TY - JOUR

T1 - T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection

AU - Musvosvi, Munyaradzi

AU - Huang, Huang

AU - Wang, Chunlin

AU - Xia, Qiong

AU - Rozot, Virginie

AU - Krishnan, Akshaya

AU - Acs, Peter

AU - Cheruku, Abhilasha

AU - Obermoser, Gerlinde

AU - Leslie, Alasdair

AU - Behar, Samuel M.

AU - Hanekom, Willem A.

AU - Bilek, Nicole

AU - Fisher, Michelle

AU - Kaufmann, Stefan H.E.

AU - Walzl, Gerhard

AU - Hatherill, Mark

AU - Davis, Mark M.

AU - Scriba, Thomas J.

AU - Kafaar, Fazlin

AU - Workman, Leslie

AU - Mulenga, Humphrey

AU - Scriba, Thomas J.

AU - Hughes, E. Jane

AU - Bilek, Nicole

AU - Erasmus, Mzwandile

AU - Nombida, Onke

AU - Veldsman, Ashley

AU - Cloete, Yolundi

AU - Abrahams, Deborah

AU - Moyo, Sizulu

AU - Gelderbloem, Sebastian

AU - Tameris, Michele

AU - Geldenhuys, Hennie

AU - Hanekom, Willem

AU - Hussey, Gregory

AU - Ehrlich, Rodney

AU - Verver, Suzanne

AU - Geiter, Larry

AU - Walzl, Gerhard

AU - Black, Gillian F.

AU - van der Spuy, Gian

AU - Stanley, Kim

AU - Kriel, Magdalena

AU - Du Plessis, Nelita

AU - Nene, Nonhlanhla

AU - Roberts, Teri

AU - Kleynhans, Leanie

AU - Gutschmidt, Andrea

AU - Smith, Bronwyn

AU - Loxton, Andre G.

AU - Chegou, Novel N.

AU - Tromp, Gerhardus

AU - Tabb, David

AU - Ottenhoff, Tom H.M.

AU - Klein, Michel R.

AU - Haks, Marielle C.

AU - Franken, Kees L.M.C.

AU - Geluk, Annemieke

AU - van Meijgaarden, Krista E.

AU - Joosten, Simone A.

AU - Boom, W. Henry

AU - Thiel, Bonnie

AU - Mayanja-Kizza, Harriet

AU - Joloba, Moses

AU - Zalwango, Sarah

AU - Nsereko, Mary

AU - Okwera, Brenda

AU - Kisingo, Hussein

AU - Kaufmann, Stefan H.E.

AU - Parida, Shreemanta K.

AU - Golinski, Robert

AU - Maertzdorf, Jeroen

AU - Weiner, January

AU - Jacobson, Marc

AU - Dockrell, Hazel M.

AU - Lalor, Maeve

AU - Smith, Steven

AU - Gorak-Stolinska, Patricia

AU - Hur, Yun Gyoung

AU - Lee, Ji Sook

AU - Crampin, Amelia C.

AU - French, Neil

AU - Ngwira, Bagrey

AU - Ben-Smith, Anne

AU - Watkins, Kate

AU - Ambrose, Lyn

AU - Simukonda, Felanji

AU - Mvula, Hazzie

AU - Chilongo, Femia

AU - Saul, Jacky

AU - Branson, Keith

AU - Suliman, Sara

AU - Scriba, Thomas J.

AU - Mahomed, Hassan

AU - Hughes, E. Jane

AU - Bilek, Nicole

AU - Erasmus, Mzwandile

AU - Nombida, Onke

AU - Veldsman, Ashley

AU - Downing, Katrina

AU - Fisher, Michelle

AU - Penn-Nicholson, Adam

AU - Mulenga, Humphrey

AU - Abel, Brian

AU - Bowmaker, Mark

AU - Kagina, Benjamin

AU - Chung, William Kwong

AU - Hanekom, Willem A.

AU - Sadoff, Jerry

AU - Sizemore, Donata

AU - Ramachandran, S.

AU - Barker, Lew

AU - Brennan, Michael

AU - Weichold, Frank

AU - Muller, Stefanie

AU - Geiter, Larry

AU - Kassa, Desta

AU - Abebe, Almaz

AU - Mesele, Tsehayenesh

AU - Tegbaru, Belete

AU - van Baarle, Debbie

AU - Miedema, Frank

AU - Howe, Rawleigh

AU - Mihret, Adane

AU - Aseffa, Abraham

AU - Bekele, Yonas

AU - Iwnetu, Rachel

AU - Tafesse, Mesfin

AU - Yamuah, Lawrence

AU - Ota, Martin

AU - Sutherland, Jayne

AU - Hill, Philip

AU - Adegbola, Richard

AU - Corrah, Tumani

AU - Antonio, Martin

AU - Togun, Toyin

AU - Adetifa, Ifedayo

AU - Donkor, Simon

AU - Andersen, Peter

AU - Rosenkrands, Ida

AU - Doherty, Mark

AU - Weldingh, Karin

AU - Schoolnik, Gary

AU - Dolganov, Gregory

AU - Van, Tran

PY - 2023/1

Y1 - 2023/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85147048278&partnerID=8YFLogxK

U2 - 10.1038/s41591-022-02110-9

DO - 10.1038/s41591-022-02110-9

M3 - Article

C2 - 36604540

AN - SCOPUS:85147048278

SN - 1078-8956

VL - 29

SP - 258

EP - 269

JO - Nature medicine

JF - Nature medicine

IS - 1

ER -

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

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