Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels.
Publication Title
Front Immunol
Document Type
Article
Publication Date
1-1-2024
Keywords
washington; swedish; isb; covid-19; Humans; COVID-19; SARS-CoV-2; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Receptors, Antigen, T-Cell; Male; Middle Aged; Female; Adult; Epitopes, T-Lymphocyte; Aged
Abstract
INTRODUCTION: T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.
METHODS: Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.
RESULTS: Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]).
DISCUSSION: The approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.
Specialty/Research Institute
Infectious Diseases
Specialty/Research Institute
Institute for Systems Biology
DOI
10.3389/fimmu.2024.1488860
