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

• DOI: 10.1073/pnas.2201541119
• Publication Date: 2022-08-09T17:33:57Z
• Authors: 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 ...; Leticia Monin; Miguel Muñoz-Ruiz; Duncan R. McKenzie; Thomas S. Hayday; Isaac Francos-Qui...; Shraddha Kamdar; Richard Davis; Vasiliki Sofra; Florencia Cano; Efstathios Theodo...; 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
• Keywords: Model organisms; 0301 basic medicine; 570; adaptive immune responses; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes; Immunology; Receptors, Antigen, T-Cell; 610; Adaptive Immunity; 03 medical and health sciences; Humans; antigen-receptor repertoires; Aged; B-Lymphocytes; 0303 health sciences; Human Biology & Physiology; SARS-CoV-2; FOS: Clinical medicine; COVID-19; Biological Sciences; 3. Good health; immunoPETE; Genetic Loci; Seroconversion; next-generation sequencing; Immunoglobulin Heavy Chains

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.