TRB sequences targeting ORF1a/b are associated with disease severity in hospitalized COVID-19 patients
| العنوان: | TRB sequences targeting ORF1a/b are associated with disease severity in hospitalized COVID-19 patients |
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| المؤلفون: | Jorn L. J. C. Assmann, Willem A. Dik, P Martijn Kolijn, Vincent H.J. van der Velden, Anton W. Langerak, Ton A.A.M. Ermens, Daan W Loth, Benjamin Schrijver, Adriaan J van Gammeren |
| المساهمون: | Immunology |
| المصدر: | Journal of Leukocyte Biology, 111(1), 283-289. John Wiley & Sons Inc. Journal of Leukocyte Biology |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | 0301 basic medicine, Time Factors, Receptors, Antigen, T-Cell, alpha-beta, Immunology, Brief Conclusive Report, Genome, Viral, Immunogenetics, Biology, medicine.disease_cause, Severity of Illness Index, Genome, SARS‐CoV‐2, DNA sequencing, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, Antigen, COVID‐19, TCR sequencing, medicine, Humans, Immunology and Allergy, Amino Acid Sequence, T-Cell Receptor Beta Chain, Aged, Polyproteins, Genetics, SARS-CoV-2, Repertoire, COVID-19, Cell Biology, Immune dysregulation, Acquired immune system, Complementarity Determining Regions, immunogenetics, Hospitalization, 030104 developmental biology, 030220 oncology & carcinogenesis |
| الوصف: | 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. Graphical Abstract The T cell receptor beta chain (TRB) repertoire of hospitalized COVID‐19 patients revealed that TRB sequences targeting nonstructural proteins of SARS‐CoV‐2 may negatively affect disease severity. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0741-5400 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::adb3c5d2260e4f303c1dc9b988c60693 http://www.scopus.com/inward/record.url?scp=85104258106&partnerID=8YFLogxK |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....adb3c5d2260e4f303c1dc9b988c60693 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 07415400 |
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