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

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journal contribution
posted on 2022-08-15, 10:24 authored by 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
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.


Crick (Grant ID: 10093, Grant title: Hayday FC001093)


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