TRB sequences targeting ORF1a/b are associated with disease severity in hospitalized COVID-19 patients

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Jorn L.J.C. Assmann¹  P. Martijn Kolijn¹  Benjamin Schrijver¹  Adriaan J. van Gammeren²  Daan W. Loth³  Ton A.A.M. Ermens²  Willem A. Dik¹  Vincent H.J. van der Velden¹  Anton W. Langerak¹ 

[1] Department of Immunology, Laboratory Medical Immunology, Erasmus MC University Medical Center;Department of Clinical Chemistry and Hematology, Amphia Hospital;Department of Pulmonology, Amphia Hospital

关键词: COVID-19;    immunogenetics;    SARS-CoV-2;    TCR sequencing;   

DOI  :  10.1002/JLB.6COVCRA1120-762R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T lymphocyte response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to disease course severity. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 781 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 158 SARS-CoV-2 specific TRB sequences belonging to 134 clusters in our COVID-19 patients. Next, we investigated 113 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences toward the nonstructural proteins (NSPs) encoded within ORF1a/b of the SARS-CoV-2 genome was observed in clusters associated with critical disease course when compared to COVID-19 clusters associated with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from NSPs of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.

【 授权许可】

CC BY