ArticlemedRxiv : the preprint server for health sciences2020
Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels.
Article in medRxiv : the preprint server for health sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 233 citations in OpenAlex.
- Neural network models for sequence-based TCR and HLA association prediction.PLoS computational biology · 2023Article
- Comprehensive immune profiling of SARS-CoV-2 infected kidney transplant patients.Frontiers in transplantation · 2023Article
- Article
- Large-scale analysis of SARS-CoV-2 spike-glycoprotein mutants demonstrates the need for continuous screening of virus isolates.PloS one · 2021Article
- Most Japanese individuals are genetically predisposed to recognize an immunogenic protein fragment shared between COVID-19 and common cold coronaviruses.F1000Research · 2021Article
- Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.PloS one · 2021Article
- Shared CD8Nature reviews. Immunology · 2020Article
- An Effective COVID-19 Vaccine Needs to Engage T Cells.Frontiers in immunology · 2020Article
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Authors and funding
56 authors at 10 institutions in 2 countries.
Funding
Abstract
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. 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 (class II data in a forthcoming study). 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. 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]). These results demonstrate an approach to reliably assess the adaptive immune response both soon after viral antigenic exposure (before antibodies are typically detectable) as well as at later time points. This blood-based molecular approach to characterizing the cellular immune response has applications in clinical diagnostics as well as in vaccine development and monitoring.
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Registered trials
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