Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection

TL;DR

This study uses longitudinal high-throughput TCR sequencing to analyze T cell responses and memory formation after mild COVID-19, revealing transient clonal expansions, antigen specificity, and pre-existing cross-reactive T cells.

Contribution

It provides detailed insights into the dynamics, specificity, and memory development of T cell responses to SARS-CoV-2 using longitudinal TCR sequencing.

Findings

Identification of transient T cell clonal expansions post-infection

Confirmation of SARS-CoV-2 epitope specificity of TCRs

Detection of pre-existing cross-reactive memory T cells

Abstract

COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor (TCR) sequencing to track changes in the T cell repertoire following two mild cases of COVID-19. In both donors we identified CD4+ and CD8+ T cell clones with transient clonal expansion after infection. The antigen specificity of CD8+ TCR sequences to SARS-CoV-2 epitopes was confirmed by both MHC tetramer binding and presence in large database of SARS-CoV-2 epitope-specific TCRs. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T cell clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.