tetano
Editor, Senior Moderator
Front Immunol
. 2025 Jan 7:15:1488860.
doi: 10.3389/fimmu.2024.1488860. eCollection 2024. Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels
Thomas M Snyder[SUP] #[/SUP][SUP] 1 [/SUP], Rachel M Gittelman[SUP] #[/SUP][SUP] 1 [/SUP], Mark Klinger[SUP] 1 [/SUP], Damon H May[SUP] 1 [/SUP], Edward J Osborne[SUP] 1 [/SUP], Ruth Taniguchi[SUP] 1 [/SUP], H Jabran Zahid[SUP] 2 [/SUP], Ian M Kaplan[SUP] 1 [/SUP], Jennifer N Dines[SUP] 1 [/SUP], Matthew T Noakes[SUP] 1 [/SUP], Ravi Pandya[SUP] 2 [/SUP], Xiaoyu Chen[SUP] 1 [/SUP], Summer Elasady[SUP] 1 [/SUP], Emily Svejnoha[SUP] 1 [/SUP], Peter Ebert[SUP] 1 [/SUP], Mitchell W Pesesky[SUP] 1 [/SUP], Patricia De Almeida[SUP] 1 [/SUP], Hope O'Donnell[SUP] 1 [/SUP], Quinn DeGottardi[SUP] 1 [/SUP], Gladys Keitany[SUP] 1 [/SUP], Jennifer Lu[SUP] 1 [/SUP], Allen Vong[SUP] 1 [/SUP], Rebecca Elyanow[SUP] 1 [/SUP], Paul Fields[SUP] 1 [/SUP], Hussein Al-Asadi[SUP] 1 [/SUP], Julia Greissl[SUP] 2 [/SUP], Lance Baldo[SUP] 1 [/SUP], Simona Semprini[SUP] 3 [/SUP], Claudio Cerchione[SUP] 4 [/SUP], Fabio Nicolini[SUP] 5 [/SUP], Massimiliano Mazza[SUP] 5 [/SUP], Ottavia M Delmonte[SUP] 6 [/SUP], Kerry Dobbs[SUP] 6 [/SUP], Rocio Laguna-Goya[SUP] 7 [/SUP], Gonzalo Carreño-Tarragona[SUP] 8 [/SUP], Santiago Barrio[SUP] 8 [/SUP], Luisa Imberti[SUP] 9 [/SUP], Alessandra Sottini[SUP] 9 [/SUP], Eugenia Quiros-Roldan[SUP] 9 [/SUP], Camillo Rossi[SUP] 9 [/SUP], Andrea Biondi[SUP] 10 [/SUP], Laura Rachele Bettini[SUP] 10 [/SUP], Mariella D'Angio[SUP] 10 [/SUP], Paolo Bonfanti[SUP] 11 [/SUP], Miranda F Tompkins[SUP] 12 [/SUP], Camille Alba[SUP] 12 [/SUP], Clifton Dalgard[SUP] 13 [/SUP], Vittorio Sambri[SUP] 3 [/SUP], Giovanni Martinelli[SUP] 4 [/SUP], Jason D Goldman[SUP] 14 15 [/SUP], James R Heath[SUP] 16 [/SUP], Helen C Su[SUP] 6 [/SUP], Luigi D Notarangelo[SUP] 6 [/SUP], Estela Paz-Artal[SUP] 7 [/SUP], Joaquin Martinez-Lopez[SUP] 8 [/SUP], Bryan Howie[SUP] 1 [/SUP], Jonathan M Carlson[SUP] 2 [/SUP], Harlan S Robins[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; T cell; TCR repertoire; cellular immunity; immune response.
. 2025 Jan 7:15:1488860.
doi: 10.3389/fimmu.2024.1488860. eCollection 2024. Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels
Thomas M Snyder[SUP] #[/SUP][SUP] 1 [/SUP], Rachel M Gittelman[SUP] #[/SUP][SUP] 1 [/SUP], Mark Klinger[SUP] 1 [/SUP], Damon H May[SUP] 1 [/SUP], Edward J Osborne[SUP] 1 [/SUP], Ruth Taniguchi[SUP] 1 [/SUP], H Jabran Zahid[SUP] 2 [/SUP], Ian M Kaplan[SUP] 1 [/SUP], Jennifer N Dines[SUP] 1 [/SUP], Matthew T Noakes[SUP] 1 [/SUP], Ravi Pandya[SUP] 2 [/SUP], Xiaoyu Chen[SUP] 1 [/SUP], Summer Elasady[SUP] 1 [/SUP], Emily Svejnoha[SUP] 1 [/SUP], Peter Ebert[SUP] 1 [/SUP], Mitchell W Pesesky[SUP] 1 [/SUP], Patricia De Almeida[SUP] 1 [/SUP], Hope O'Donnell[SUP] 1 [/SUP], Quinn DeGottardi[SUP] 1 [/SUP], Gladys Keitany[SUP] 1 [/SUP], Jennifer Lu[SUP] 1 [/SUP], Allen Vong[SUP] 1 [/SUP], Rebecca Elyanow[SUP] 1 [/SUP], Paul Fields[SUP] 1 [/SUP], Hussein Al-Asadi[SUP] 1 [/SUP], Julia Greissl[SUP] 2 [/SUP], Lance Baldo[SUP] 1 [/SUP], Simona Semprini[SUP] 3 [/SUP], Claudio Cerchione[SUP] 4 [/SUP], Fabio Nicolini[SUP] 5 [/SUP], Massimiliano Mazza[SUP] 5 [/SUP], Ottavia M Delmonte[SUP] 6 [/SUP], Kerry Dobbs[SUP] 6 [/SUP], Rocio Laguna-Goya[SUP] 7 [/SUP], Gonzalo Carreño-Tarragona[SUP] 8 [/SUP], Santiago Barrio[SUP] 8 [/SUP], Luisa Imberti[SUP] 9 [/SUP], Alessandra Sottini[SUP] 9 [/SUP], Eugenia Quiros-Roldan[SUP] 9 [/SUP], Camillo Rossi[SUP] 9 [/SUP], Andrea Biondi[SUP] 10 [/SUP], Laura Rachele Bettini[SUP] 10 [/SUP], Mariella D'Angio[SUP] 10 [/SUP], Paolo Bonfanti[SUP] 11 [/SUP], Miranda F Tompkins[SUP] 12 [/SUP], Camille Alba[SUP] 12 [/SUP], Clifton Dalgard[SUP] 13 [/SUP], Vittorio Sambri[SUP] 3 [/SUP], Giovanni Martinelli[SUP] 4 [/SUP], Jason D Goldman[SUP] 14 15 [/SUP], James R Heath[SUP] 16 [/SUP], Helen C Su[SUP] 6 [/SUP], Luigi D Notarangelo[SUP] 6 [/SUP], Estela Paz-Artal[SUP] 7 [/SUP], Joaquin Martinez-Lopez[SUP] 8 [/SUP], Bryan Howie[SUP] 1 [/SUP], Jonathan M Carlson[SUP] 2 [/SUP], Harlan S Robins[SUP] 1 [/SUP]
Affiliations
- PMID: 39840037
- PMCID: PMC11747429
- DOI: 10.3389/fimmu.2024.1488860
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.
Keywords: COVID-19; SARS-CoV-2; T cell; TCR repertoire; cellular immunity; immune response.