T cell receptor sequences are the dominant factor contributing to the phenotype of CD8+ T cells with specificities against immunogenic viral antigens

Abstract

Antigen-specific CD8+ Tcells mediate pathogen clearance. Tcell phenotype is influenced by Tcell receptor (TCR) sequences and environmental signals. Quantitative comparisons of these factors in human disease, while challenging to obtain, can provide foundational insights into basic Tcell biology. Here, we investigate the phenotype kinetics of 679 CD8+ Tcell clonotypes, each with specificity against one of three immunogenic viral antigens. Data were collected from a longitudinal study of 68 COVID-19 patients with antigens from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cytomegalovirus (CMV), and influenza. Each antigen is associated with a different type of immune activation during COVID-19. We find TCR sequence to be by far the most important factor in shaping Tcell phenotype and persistence for populations specific to any of these antigens. Our work demonstrates the important relationship between TCR sequence and Tcell phenotype and persistence and helps explain why Tcell phenotype often appears to be determined early in an infection.