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.
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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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