Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19More about Open Access at the Crick
Authors listMagdalene 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 Aldama Miguel Munoz-Ruiz Duncan 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 Hayday
Toggle all authors (41)
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.
Issue number 34