RT Journal Article
SR Electronic
T1 Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.09.289355
DO 10.1101/2020.09.09.289355
A1 Anna Postovskaya
A1 Alexandra Vujkovic
A1 Tessa de Block
A1 Lida van Petersen
A1 Maartje van Frankenhuijsen
A1 Isabel Brosius
A1 Emmanuel Bottieau
A1 Christophe Van Dijck
A1 Caroline Theunissen
A1 Sabrina H. van Ierssel
A1 Erika Vlieghe
A1 Esther Bartholomeus
A1 Wim Adriaensen
A1 Guido Vanham
A1 Benson Ogunjimi
A1 Kris Laukens
A1 Koen Vercauteren
A1 Pieter Meysman
YR 2023
UL http://biorxiv.org/content/early/2023/01/09/2020.09.09.289355.abstract
AB Despite the general agreement on the importance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain, while this knowledge may indicate how to adjust vaccines and maintain robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to epitopes unique to SARS-CoV-2 (SC-unique) or shared with other coronaviruses (CoV-common), we trained a large number of TCR-epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. Applying those models to longitudinal COVID-19 TCR repertoires of critical and non-critical COVID-19 patients, we discovered that notwithstanding comparable CD8+ T-cell depletion and the sizes of putative CoV-common CD8+ TCR repertoires in all symptomatic patients at the initial stage of the disease, the temporal dynamics of putative SC2-unique TCRs differed depending on the disease severity. Only non-critical patients had developed large and diverse SC2-unique CD8+ T-cell response by the second week of the disease. Additionally, only this patient group demonstrated redundancy in CD8+ TCRs putatively recognizing unique and common SARS-CoV-2 epitopes. Our findings thus emphasize the role of the de novo CD8+ T-cell response and support the argument against the clinical benefit of pre-existing cross-reactive CD8+ T cells. Now, the analytical framework of this study can not only be employed to track specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire but also be generalized to more epitopes and be employed for adaptive immune response assessment and monitoring to inform public health decisions.Competing Interest StatementPM, KL, BO hold shares of ImmuneWatch BV, an immunoinformatics company.