Diagnosing viral infections through T-cell receptor sequencing of activated CD8+ T cells

A Vujkovic, M Ha, T de Block, L van Petersen, I Brosius, C Theunissen, SH van Ierssel, E Bartholomeus, W Adriaensen, G Vanham, G Elias, Pierre Van Damme, Viggo Van Tendeloo, Philippe Beutels, M van Frankenhuijsen, E Vlieghe, B Ogunjimi, Kris Laukens, P Meysman, K Vercauteren

Research output: Contribution to journalA1: Web of Science-articlepeer-review


T-cell–based diagnostic tools identify pathogen exposure but lack differentiation between recent and historical exposures in acute infectious diseases. Here, T-cell receptor (TCR) RNA sequencing was performed on HLA-DR+/CD38+CD8+ T-cell subsets of hospitalized coronavirus disease 2019 (COVID-19) patients (n = 30) and healthy controls (n = 30; 10 of whom had previously been exposed to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). CDR3α and CDR3β TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2–associated CDR3α and CDR3β sequences corresponding to >1000 SARS-CoV-2 epitopes. The depth of the SARS-CoV-2–associated CDR3α/β sequences differentiated COVID-19 patients from the healthy controls with a receiver operating characteristic area under the curve of 0.84 ± 0.10. Hence, annotating TCR sequences of activated CD8+ T cells can be used to diagnose an acute viral infection and discriminate it from historical exposure. In essence, this work presents a new paradigm for applying the T-cell repertoire to accomplish TCR-based diagnostics.
Original languageEnglish
JournalJournal of Infectious Diseases
Issue number2
Pages (from-to)507-516
Number of pages10
Publication statusPublished - 2024


  • COVID-19
  • NGS-based diagnostics
  • T cells
  • TCR sequencing
  • Immunoinformatics
  • Immunology


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