Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels
IntroductionT 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.MethodsHere, we combined two...
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2025-01-01
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| author | Thomas M. Snyder Rachel M. Gittelman Mark Klinger Damon H. May Edward J. Osborne Ruth Taniguchi H. Jabran Zahid Ian M. Kaplan Jennifer N. Dines Matthew T. Noakes Ravi Pandya Xiaoyu Chen Summer Elasady Emily Svejnoha Peter Ebert Mitchell W. Pesesky Patricia De Almeida Hope O’Donnell Quinn DeGottardi Gladys Keitany Jennifer Lu Allen Vong Rebecca Elyanow Paul Fields Hussein Al-Asadi Julia Greissl Lance Baldo Simona Semprini Claudio Cerchione Fabio Nicolini Massimiliano Mazza Ottavia M. Delmonte Kerry Dobbs Rocio Laguna-Goya Gonzalo Carreño-Tarragona Santiago Barrio Luisa Imberti Alessandra Sottini Eugenia Quiros-Roldan Camillo Rossi Andrea Biondi Laura Rachele Bettini Mariella D’Angio Paolo Bonfanti Miranda F. Tompkins Camille Alba Clifton Dalgard Vittorio Sambri Giovanni Martinelli Jason D. Goldman Jason D. Goldman James R. Heath Helen C. Su Luigi D. Notarangelo Estela Paz-Artal Joaquin Martinez-Lopez Bryan Howie Jonathan M. Carlson Harlan S. Robins |
| author_facet | Thomas M. Snyder Rachel M. Gittelman Mark Klinger Damon H. May Edward J. Osborne Ruth Taniguchi H. Jabran Zahid Ian M. Kaplan Jennifer N. Dines Matthew T. Noakes Ravi Pandya Xiaoyu Chen Summer Elasady Emily Svejnoha Peter Ebert Mitchell W. Pesesky Patricia De Almeida Hope O’Donnell Quinn DeGottardi Gladys Keitany Jennifer Lu Allen Vong Rebecca Elyanow Paul Fields Hussein Al-Asadi Julia Greissl Lance Baldo Simona Semprini Claudio Cerchione Fabio Nicolini Massimiliano Mazza Ottavia M. Delmonte Kerry Dobbs Rocio Laguna-Goya Gonzalo Carreño-Tarragona Santiago Barrio Luisa Imberti Alessandra Sottini Eugenia Quiros-Roldan Camillo Rossi Andrea Biondi Laura Rachele Bettini Mariella D’Angio Paolo Bonfanti Miranda F. Tompkins Camille Alba Clifton Dalgard Vittorio Sambri Giovanni Martinelli Jason D. Goldman Jason D. Goldman James R. Heath Helen C. Su Luigi D. Notarangelo Estela Paz-Artal Joaquin Martinez-Lopez Bryan Howie Jonathan M. Carlson Harlan S. Robins |
| author_sort | Thomas M. Snyder |
| collection | DOAJ |
| description | IntroductionT 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.MethodsHere, 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.ResultsCollectively, 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]).DiscussionThe 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. |
| format | Article |
| id | doaj-art-f8f573fc5812425fb44dc5a97ac492c3 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-f8f573fc5812425fb44dc5a97ac492c32025-01-07T06:47:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14888601488860Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levelsThomas M. Snyder0Rachel M. Gittelman1Mark Klinger2Damon H. May3Edward J. Osborne4Ruth Taniguchi5H. Jabran Zahid6Ian M. Kaplan7Jennifer N. Dines8Matthew T. Noakes9Ravi Pandya10Xiaoyu Chen11Summer Elasady12Emily Svejnoha13Peter Ebert14Mitchell W. Pesesky15Patricia De Almeida16Hope O’Donnell17Quinn DeGottardi18Gladys Keitany19Jennifer Lu20Allen Vong21Rebecca Elyanow22Paul Fields23Hussein Al-Asadi24Julia Greissl25Lance Baldo26Simona Semprini27Claudio Cerchione28Fabio Nicolini29Massimiliano Mazza30Ottavia M. Delmonte31Kerry Dobbs32Rocio Laguna-Goya33Gonzalo Carreño-Tarragona34Santiago Barrio35Luisa Imberti36Alessandra Sottini37Eugenia Quiros-Roldan38Camillo Rossi39Andrea Biondi40Laura Rachele Bettini41Mariella D’Angio42Paolo Bonfanti43Miranda F. Tompkins44Camille Alba45Clifton Dalgard46Vittorio Sambri47Giovanni Martinelli48Jason D. Goldman49Jason D. Goldman50James R. Heath51Helen C. Su52Luigi D. Notarangelo53Estela Paz-Artal54Joaquin Martinez-Lopez55Bryan Howie56Jonathan M. Carlson57Harlan S. Robins58Adaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesMicrosoft Research, Redmond, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesMicrosoft Research, Redmond, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesMicrosoft Research, Redmond, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesUnit of Microbiology - The Great Romagna Hub Laboratory, Pievesestina ITALY and DIMES, University of Bologna, Bologna, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyImmunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyImmunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyImmune Deficiency Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesImmune Deficiency Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDepartment of Immunology, Hospital 12 de Octubre, CNIO, Complutense University, Madrid, SpainHematology Department, Hospital 12 de Octubre, CNIO, Complutense University, Madrid, SpainHematology Department, Hospital 12 de Octubre, CNIO, Complutense University, Madrid, SpainLaboratorio CREA, Department of Infectious and Tropical Diseases, and Medical Officer, ASST Spedali Civili di Brescia and University of Brescia, Brescia, ItalyLaboratorio CREA, Department of Infectious and Tropical Diseases, and Medical Officer, ASST Spedali Civili di Brescia and University of Brescia, Brescia, ItalyLaboratorio CREA, Department of Infectious and Tropical Diseases, and Medical Officer, ASST Spedali Civili di Brescia and University of Brescia, Brescia, ItalyLaboratorio CREA, Department of Infectious and Tropical Diseases, and Medical Officer, ASST Spedali Civili di Brescia and University of Brescia, Brescia, Italy0Department of Pediatrics and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale San Gerardo, Monza, Italy0Department of Pediatrics and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale San Gerardo, Monza, Italy0Department of Pediatrics and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale San Gerardo, Monza, Italy1Department of Infectious Diseases, University of Milano-Bicocca-Ospedale San Gerardo, Monza, Italy2The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, United States2The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, United States3Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesUnit of Microbiology - The Great Romagna Hub Laboratory, Pievesestina ITALY and DIMES, University of Bologna, Bologna, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy4Swedish Medical Center, Seattle, WA, United States5Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United States6Institute for Systems Biology, Seattle, WA, United StatesImmune Deficiency Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesImmune Deficiency Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDepartment of Immunology, Hospital 12 de Octubre, CNIO, Complutense University, Madrid, SpainHematology Department, Hospital 12 de Octubre, CNIO, Complutense University, Madrid, SpainAdaptive Biotechnologies, Seattle, WA, United StatesMicrosoft Research, Redmond, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesIntroductionT 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.MethodsHere, 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.ResultsCollectively, 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]).DiscussionThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1488860/fullSARS-CoV-2COVID-19T cellTCR repertoireimmune responsecellular immunity |
| spellingShingle | Thomas M. Snyder Rachel M. Gittelman Mark Klinger Damon H. May Edward J. Osborne Ruth Taniguchi H. Jabran Zahid Ian M. Kaplan Jennifer N. Dines Matthew T. Noakes Ravi Pandya Xiaoyu Chen Summer Elasady Emily Svejnoha Peter Ebert Mitchell W. Pesesky Patricia De Almeida Hope O’Donnell Quinn DeGottardi Gladys Keitany Jennifer Lu Allen Vong Rebecca Elyanow Paul Fields Hussein Al-Asadi Julia Greissl Lance Baldo Simona Semprini Claudio Cerchione Fabio Nicolini Massimiliano Mazza Ottavia M. Delmonte Kerry Dobbs Rocio Laguna-Goya Gonzalo Carreño-Tarragona Santiago Barrio Luisa Imberti Alessandra Sottini Eugenia Quiros-Roldan Camillo Rossi Andrea Biondi Laura Rachele Bettini Mariella D’Angio Paolo Bonfanti Miranda F. Tompkins Camille Alba Clifton Dalgard Vittorio Sambri Giovanni Martinelli Jason D. Goldman Jason D. Goldman James R. Heath Helen C. Su Luigi D. Notarangelo Estela Paz-Artal Joaquin Martinez-Lopez Bryan Howie Jonathan M. Carlson Harlan S. Robins Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels Frontiers in Immunology SARS-CoV-2 COVID-19 T cell TCR repertoire immune response cellular immunity |
| title | Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels |
| title_full | Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels |
| title_fullStr | Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels |
| title_full_unstemmed | Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels |
| title_short | Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels |
| title_sort | magnitude and dynamics of the t cell response to sars cov 2 infection at both individual and population levels |
| topic | SARS-CoV-2 COVID-19 T cell TCR repertoire immune response cellular immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1488860/full |
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