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

Joseph, M; Wu, Y; Dannebaum, R; Rubelt, F; Zlatareva, I; Lorenc, A; Du, ZG; ... Hayday, AC; + view all (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) , Article e2201541119. 10.1073/pnas.2201541119. Green open access

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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.

Type: Article
Title: Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.2201541119
Publisher version: https://doi.org/10.1073/pnas.2201541119
Language: English
Additional information: © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/).
Keywords: next-generation sequencing, antigen-receptor repertoires, SARS-CoV-2, adaptive immune responses, immunoPETE
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10156491
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