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 journalArticlepeer-review

7 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 languageEnglish
Article numbere2201541119
Pages (from-to)e2201541119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number34
DOIs
Publication statusPublished - 23 Aug 2022

Keywords

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

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