Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19

Magdalene Joseph; Yin Wu; Richard Dannebaum; Florian Rubelt; Iva Zlatareva; Anna Lorenc; Zhipei Gracie Du; Daniel Davies; Fernanda Kyle-Cezar; Abhishek Das; Sarah Gee; Jeffrey Seow; Carl Graham; Dilduz Telman; Clara Bermejo; Hai Lin; Hosseinali Asgharian; Adam G. Laing; Irene Del Molino Del Barrio; Leticia Monin; Miguel Muñoz-Ruiz; Duncan R. McKenzie; Thomas S. Hayday; Isaac Francos-Quijorna; Shraddha Kamdar; Richard Davis; Vasiliki Sofra; Florencia Cano; Efstathios Theodoridis; Lauren Martinez; Blair Merrick; Karen Bisnauthsing; Kate Brooks; Jonathan Edgeworth; John Cason; Christine Mant; Katie J. Doores; Pierre Vantourout; Khai Luong; Jan Berka; Adrian C. Hayday

doi:10.1073/pnas.2201541119

Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19

Magdalene Joseph, Yin Wu, Richard Dannebaum, Florian Rubelt, Iva Zlatareva, Anna Lorenc, Zhipei Gracie Du, Daniel Davies, Fernanda Kyle-Cezar, Abhishek Das, Sarah Gee, Jeffrey Seow, Carl Graham, Dilduz Telman, Clara Bermejo, Hai Lin, Hosseinali Asgharian, Adam G. Laing, Irene Del Molino Del Barrio, Leticia MoninMiguel Muñoz-Ruiz, Duncan R. McKenzie, Thomas S. Hayday, Isaac Francos-Quijorna, Shraddha Kamdar, Richard Davis, Vasiliki Sofra, Florencia Cano, Efstathios Theodoridis, Lauren Martinez, Blair Merrick, Karen Bisnauthsing, Kate Brooks, Jonathan Edgeworth, John Cason, Christine Mant, Katie J. Doores, Pierre Vantourout, Khai Luong, Jan Berka, Adrian C. Hayday

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

9 Citations (Scopus)

Abstract

Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.

Original language	English
Article number	e2201541119
Pages (from-to)	e2201541119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	34
DOIs	https://doi.org/10.1073/pnas.2201541119
Publication status	Published - 23 Aug 2022

Keywords

adaptive immune responses
antigen-receptor repertoires
immunoPETE
next-generation sequencing
SARS-CoV-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1073/pnas.2201541119

Cite this

Joseph, M., Wu, Y., Dannebaum, R., Rubelt, F., Zlatareva, I., Lorenc, A., Du, Z. G., Davies, D., Kyle-Cezar, F., Das, A., Gee, S., Seow, J., Graham, C., Telman, D., Bermejo, C., Lin, H., Asgharian, H., Laing, A. G., Del Molino Del Barrio, I., ... Hayday, A. C. (2022). Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19. Proceedings of the National Academy of Sciences of the United States of America, 119(34), e2201541119. Article e2201541119. https://doi.org/10.1073/pnas.2201541119

@article{0c307092a4d0436caef99ba30dbbaf07,

title = "Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19",

abstract = "Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.",

keywords = "adaptive immune responses, antigen-receptor repertoires, immunoPETE, next-generation sequencing, SARS-CoV-2",

author = "Magdalene Joseph and Yin Wu and Richard Dannebaum and Florian Rubelt and Iva Zlatareva and Anna Lorenc and Du, {Zhipei Gracie} and Daniel Davies and Fernanda Kyle-Cezar and Abhishek Das and Sarah Gee and Jeffrey Seow and Carl Graham and Dilduz Telman and Clara Bermejo and Hai Lin and Hosseinali Asgharian and Laing, {Adam G.} and {Del Molino Del Barrio}, Irene and Leticia Monin and Miguel Mu{\~n}oz-Ruiz and McKenzie, {Duncan R.} and Hayday, {Thomas S.} and Isaac Francos-Quijorna and Shraddha Kamdar and Richard Davis and Vasiliki Sofra and Florencia Cano and Efstathios Theodoridis and Lauren Martinez and Blair Merrick and Karen Bisnauthsing and Kate Brooks and Jonathan Edgeworth and John Cason and Christine Mant and Doores, {Katie J.} and Pierre Vantourout and Khai Luong and Jan Berka and Hayday, {Adrian C.}",

note = "Funding Information: ACKNOWLEDGMENTS. We thank all patients and blood donors who participated in this study, as well as the medical and research teams at Guy{\textquoteright}s and St. Thomas{\textquoteright} Hospitals. Schema figures were created with BioRender.com. We likewise thank our colleagues for discussions and for their support. This study was supported by a Cancer Research Institute Irvington Fellowship (D.R.M.); Cancer Research UK (CRUK) Cancer ImmunoTherapy Accelerator (A.C.H., I.D.M.D.B.); CRUK City of London Major Cancer Centre studentship C604/A27440 (M.J.); European Molecular Biology Organization Long-term Fellowship 198-2018 (M.M.R.); Francis Crick Institute, which receives core funding from CRUK (grant FC001093), Medical Research Council (MRC) grant FC001093, and the Wellcome Trust (grant FC001093; A.C.H., L. Monin, and F.C.); John Black Charitable Foundation (A.C.H.); King{\textquoteright}s Together Rapid COVID-19 Call Award (K.J.D.); King{\textquoteright}s Together Seed Fund (A.C.H.); MRC King{\textquoteright}s College London Doctoral Training Partnership in Biomedical Sciences grant MR/N013700/1 (C.G., S.G.); National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship (A.D. and Y.W.); NIHR Biomedical Research Centre for the Infectious Diseases Biobank (J.C. and C.M.); Rosetrees Trust (A.C.H.); Wellcome Trust grant 106292/Z/14/Z (A.C.H., P.V., I.Z., and V.S.); Wellcome Trust Clinical Research Career Development Fellowship 220589/Z/20/Z (Y.W.); and UK COVID-Immunology-Consortium grant C33499/A20265 (A.C.H.) Funding Information: We thank all patients and blood donors who participated in this study, as well as the medical and research teams at Guy{\textquoteright}s and St. Thomas{\textquoteright} Hospitals. Schema figures were created with BioRender.com. We likewise thank our colleagues for discussions and for their support. This study was supported by a Cancer Research Institute Irvington Fellowship (D.R.M.); Cancer Research UK (CRUK) Cancer ImmunoTherapy Accelerator (A.C.H., I.D.M.D.B.); CRUK City of London Major Cancer Centre studentship C604/A27440 (M.J.); European Molecular Biology Organization Long-term Fellowship 198-2018 (M.M.R.); Francis Crick Institute, which receives core funding from CRUK (grant FC001093), Medical Research Council (MRC) grant FC001093, and the Wellcome Trust (grant FC001093; A.C.H., L. Monin, and F.C.); John Black Charitable Foundation (A.C.H.); King{\textquoteright}s Together Rapid COVID-19 Call Award (K.J.D.); King{\textquoteright}s Together Seed Fund (A.C.H.); MRC King{\textquoteright}s College London Doctoral Training Partnership in Biomedical Sciences grant MR/N013700/1 (C.G., S.G.); National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship (A.D. and Y.W.); NIHR Biomedical Research Centre for the Infectious Diseases Biobank (J.C. and C.M.); Rosetrees Trust (A.C.H.); Wellcome Trust grant 106292/Z/14/Z (A.C.H., P.V., I.Z., and V.S.); Wellcome Trust Clinical Research Career Development Fellowship 220589/Z/20/Z (Y.W.); and UK COVID-Immunology-Consortium grant C33499/A20265 (A.C.H.) Publisher Copyright: Copyright {\textcopyright} 2022 the Author(s). Published by PNAS.",

year = "2022",

month = aug,

day = "23",

doi = "10.1073/pnas.2201541119",

language = "English",

volume = "119",

pages = "e2201541119",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Acad Sciences",

number = "34",

}

Joseph, M , Wu, Y, Dannebaum, R, Rubelt, F, Zlatareva, I , Lorenc, A, Du, ZG, Davies, D , Kyle-Cezar, F, Das, A, Gee, S , Seow, J , Graham, C, Telman, D, Bermejo, C, Lin, H, Asgharian, H, Laing, AG , Del Molino Del Barrio, I, Monin, L, Muñoz-Ruiz, M, McKenzie, DR, Hayday, TS , Francos-Quijorna, I , Kamdar, S, Davis, R, Sofra, V, Cano, F, Theodoridis, E, Martinez, L, Merrick, B, Bisnauthsing, K, Brooks, K, Edgeworth, J , Cason, J , Mant, C , Doores, KJ , Vantourout, P, Luong, K, Berka, J & Hayday, AC 2022, 'Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 34, e2201541119, pp. e2201541119. https://doi.org/10.1073/pnas.2201541119

Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19. / Joseph, Magdalene ; Wu, Yin; Dannebaum, Richard et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 34, e2201541119, 23.08.2022, p. e2201541119.

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

TY - JOUR

T1 - Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19

AU - Joseph, Magdalene

AU - Wu, Yin

AU - Dannebaum, Richard

AU - Rubelt, Florian

AU - Zlatareva, Iva

AU - Lorenc, Anna

AU - Du, Zhipei Gracie

AU - Davies, Daniel

AU - Kyle-Cezar, Fernanda

AU - Das, Abhishek

AU - Gee, Sarah

AU - Seow, Jeffrey

AU - Graham, Carl

AU - Telman, Dilduz

AU - Bermejo, Clara

AU - Lin, Hai

AU - Asgharian, Hosseinali

AU - Laing, Adam G.

AU - Del Molino Del Barrio, Irene

AU - Monin, Leticia

AU - Muñoz-Ruiz, Miguel

AU - McKenzie, Duncan R.

AU - Hayday, Thomas S.

AU - Francos-Quijorna, Isaac

AU - Kamdar, Shraddha

AU - Davis, Richard

AU - Sofra, Vasiliki

AU - Cano, Florencia

AU - Theodoridis, Efstathios

AU - Martinez, Lauren

AU - Merrick, Blair

AU - Bisnauthsing, Karen

AU - Brooks, Kate

AU - Edgeworth, Jonathan

AU - Cason, John

AU - Mant, Christine

AU - Doores, Katie J.

AU - Vantourout, Pierre

AU - Luong, Khai

AU - Berka, Jan

AU - Hayday, Adrian C.

N1 - Funding Information: ACKNOWLEDGMENTS. We thank all patients and blood donors who participated in this study, as well as the medical and research teams at Guy’s and St. Thomas’ Hospitals. Schema figures were created with BioRender.com. We likewise thank our colleagues for discussions and for their support. This study was supported by a Cancer Research Institute Irvington Fellowship (D.R.M.); Cancer Research UK (CRUK) Cancer ImmunoTherapy Accelerator (A.C.H., I.D.M.D.B.); CRUK City of London Major Cancer Centre studentship C604/A27440 (M.J.); European Molecular Biology Organization Long-term Fellowship 198-2018 (M.M.R.); Francis Crick Institute, which receives core funding from CRUK (grant FC001093), Medical Research Council (MRC) grant FC001093, and the Wellcome Trust (grant FC001093; A.C.H., L. Monin, and F.C.); John Black Charitable Foundation (A.C.H.); King’s Together Rapid COVID-19 Call Award (K.J.D.); King’s Together Seed Fund (A.C.H.); MRC King’s College London Doctoral Training Partnership in Biomedical Sciences grant MR/N013700/1 (C.G., S.G.); National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship (A.D. and Y.W.); NIHR Biomedical Research Centre for the Infectious Diseases Biobank (J.C. and C.M.); Rosetrees Trust (A.C.H.); Wellcome Trust grant 106292/Z/14/Z (A.C.H., P.V., I.Z., and V.S.); Wellcome Trust Clinical Research Career Development Fellowship 220589/Z/20/Z (Y.W.); and UK COVID-Immunology-Consortium grant C33499/A20265 (A.C.H.) Funding Information: We thank all patients and blood donors who participated in this study, as well as the medical and research teams at Guy’s and St. Thomas’ Hospitals. Schema figures were created with BioRender.com. We likewise thank our colleagues for discussions and for their support. This study was supported by a Cancer Research Institute Irvington Fellowship (D.R.M.); Cancer Research UK (CRUK) Cancer ImmunoTherapy Accelerator (A.C.H., I.D.M.D.B.); CRUK City of London Major Cancer Centre studentship C604/A27440 (M.J.); European Molecular Biology Organization Long-term Fellowship 198-2018 (M.M.R.); Francis Crick Institute, which receives core funding from CRUK (grant FC001093), Medical Research Council (MRC) grant FC001093, and the Wellcome Trust (grant FC001093; A.C.H., L. Monin, and F.C.); John Black Charitable Foundation (A.C.H.); King’s Together Rapid COVID-19 Call Award (K.J.D.); King’s Together Seed Fund (A.C.H.); MRC King’s College London Doctoral Training Partnership in Biomedical Sciences grant MR/N013700/1 (C.G., S.G.); National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship (A.D. and Y.W.); NIHR Biomedical Research Centre for the Infectious Diseases Biobank (J.C. and C.M.); Rosetrees Trust (A.C.H.); Wellcome Trust grant 106292/Z/14/Z (A.C.H., P.V., I.Z., and V.S.); Wellcome Trust Clinical Research Career Development Fellowship 220589/Z/20/Z (Y.W.); and UK COVID-Immunology-Consortium grant C33499/A20265 (A.C.H.) Publisher Copyright: Copyright © 2022 the Author(s). Published by PNAS.

PY - 2022/8/23

Y1 - 2022/8/23

N2 - Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.

AB - Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.

KW - adaptive immune responses

KW - antigen-receptor repertoires

KW - immunoPETE

KW - next-generation sequencing

KW - SARS-CoV-2

UR - http://www.scopus.com/inward/record.url?scp=85135769074&partnerID=8YFLogxK

U2 - 10.1073/pnas.2201541119

DO - 10.1073/pnas.2201541119

M3 - Article

C2 - 35943978

AN - SCOPUS:85135769074

SN - 0027-8424

VL - 119

SP - e2201541119

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 34

M1 - e2201541119

ER -

Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19

Abstract

Keywords

UN SDGs

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