Patterns of restricted TCR usage following SARS-CoV-2 vaccination and severe disease

作者：Emily Parsons, Zhongyan Lu, Stephanie A Richard, Amanda E Zelkoski, Jennifer Lê, Naraen Palanikumar, Phuong Nguyen, Camille Alba, Gauthaman Sukumar, John Rosenberger, Xijun Zhang, Timothy H. Burgess, Rhonda E Colombo, Katrin Mende, Catherine M Berjohn, Nusrat J Epsi, Brian K. Agan, David R. Tribble, David A Lindholm, Clifton L. Dalgard, Simon Pollett, Allison M. W. Malloy, EPICC COVID-19 Cohort Study Group · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1576903 · 被引用次数：1 · 研究领域：vaccines and immunoinformatics approaches、Immune responses and vaccinations、T-cell and B-cell Immunology

Introduction: T cells influence COVID-19 severity and establish long-lasting immune memory in response to vaccination and infection. The diversity of the T cell repertoire, and complexity of T cell epitope recognition, make it challenging to define protective epitope-specific T cells. In this study, we created a highly specific TCR meta-database to identify T cell epitopes from the nearly complete SARS-CoV-2 proteome and determine whether vaccination with mRNA vaccines influenced the TCR repertoire. Methods: Using this meta-database, we analyzed immunosequencing data of genomic DNA to define the variable region of T cell receptor (TCR) b chain (TCRB) sequences among participants in a longitudinal COVID-19 cohort study. The TCR repertoire was compared between participants who were vaccinated or unvaccinated against SARS-CoV-2 and stratified by disease severity. TCR diversity was measured using clonality, an index defined as the inverted normalized Shannon entropy. Results: Highly clonal TCR repertoires correlated with age and comorbidities. Using our meta-database approach, we found that vaccinated participants hospitalized with infection had the most restricted SARS-CoV-2-specific CD8 TCR repertoire. However, TCRB with predicted specificity to non-spike SARS-CoV-2 proteins dominated the response, even in vaccinated participants. We identified a peptide sequence in the ORF10 accessory protein that was more frequently recognized in study participants with mild disease. Converse...