Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels.

Autor: Snyder TM; Adaptive Biotechnologies, Seattle, WA, USA., Gittelman RM; Adaptive Biotechnologies, Seattle, WA, USA., Klinger M; Adaptive Biotechnologies, Seattle, WA, USA., May DH; Adaptive Biotechnologies, Seattle, WA, USA., Osborne EJ; Adaptive Biotechnologies, Seattle, WA, USA., Taniguchi R; Adaptive Biotechnologies, Seattle, WA, USA., Zahid HJ; Microsoft Research, Redmond, WA, USA., Kaplan IM; Adaptive Biotechnologies, Seattle, WA, USA., Dines JN; Adaptive Biotechnologies, Seattle, WA, USA., Noakes MT; Adaptive Biotechnologies, Seattle, WA, USA., Pandya R; Microsoft Research, Redmond, WA, USA., Chen X; Adaptive Biotechnologies, Seattle, WA, USA., Elasady S; Adaptive Biotechnologies, Seattle, WA, USA., Svejnoha E; Adaptive Biotechnologies, Seattle, WA, USA., Ebert P; Adaptive Biotechnologies, Seattle, WA, USA., Pesesky MW; Adaptive Biotechnologies, Seattle, WA, USA., De Almeida P; Adaptive Biotechnologies, Seattle, WA, USA., O'Donnell H; Adaptive Biotechnologies, Seattle, WA, USA., DeGottardi Q; Adaptive Biotechnologies, Seattle, WA, USA., Keitany G; Adaptive Biotechnologies, Seattle, WA, USA., Lu J; Adaptive Biotechnologies, Seattle, WA, USA., Vong A; Adaptive Biotechnologies, Seattle, WA, USA., Elyanow R; Adaptive Biotechnologies, Seattle, WA, USA., Fields P; Adaptive Biotechnologies, Seattle, WA, USA., Greissl J; Microsoft Research, Redmond, WA, USA., Baldo L; Adaptive Biotechnologies, Seattle, WA, USA., Semprini S; Unit of Microbiology - The Great Romagna Hub Laboratory, Pievesestina ITALY and DIMES, University of Bologna, Bologna, Italy., Cerchione C; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy., Nicolini F; Immunotherapy, Cell Therapy and Biobank (ITCB), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy., Mazza M; Immunotherapy, Cell Therapy and Biobank (ITCB), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy., Delmonte OM; Immune Deficiency Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Dobbs K; Immune Deficiency Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Laguna-Goya R; Department of Immunology, Hospital 12 de Octubre, i+12, CNIO, Complutense University, Madrid, Spain., Carreño-Tarragona G; Hematology Department, Hospital 12 de Octubre, i+12, CNIO, Complutense University, Madrid, Spain., Barrio S; Hematology Department, Hospital 12 de Octubre, i+12, CNIO, Complutense University, Madrid, Spain., Imberti L; Laboratorio CREA, Department of Infectious and Tropical Diseases, and Medical Officer, ASST Spedali Civili di Brescia and University of Brescia, Brescia, Italy., Sottini A; Laboratorio CREA, Department of Infectious and Tropical Diseases, and Medical Officer, ASST Spedali Civili di Brescia and University of Brescia, Brescia, Italy., Quiros-Roldan E; Laboratorio CREA, Department of Infectious and Tropical Diseases, and Medical Officer, ASST Spedali Civili di Brescia and University of Brescia, Brescia, Italy., Rossi C; Laboratorio CREA, Department of Infectious and Tropical Diseases, and Medical Officer, ASST Spedali Civili di Brescia and University of Brescia, Brescia, Italy., Biondi A; Department of Pediatrics and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale San Gerardo, Monza, IT., Bettini LR; Department of Pediatrics and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale San Gerardo, Monza, IT., D'Angio M; Department of Pediatrics and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale San Gerardo, Monza, IT., Bonfanti P; Department of Infectious Diseases, University of Milano-Bicocca-Ospedale San Gerardo, Monza, IT., Tompkins MF; The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Alba C; The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Dalgard C; Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Sambri V; Unit of Microbiology - The Great Romagna Hub Laboratory, Pievesestina ITALY and DIMES, University of Bologna, Bologna, Italy., Martinelli G; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy., Goldman JD; Swedish Medical Center, Seattle, WA, USA, and Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA., Heath JR; Institute for Systems Biology, Seattle, WA, USA., Su HC; Immune Deficiency Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Notarangelo LD; Immune Deficiency Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Paz-Artal E; Department of Immunology, Hospital 12 de Octubre, i+12, CNIO, Complutense University, Madrid, Spain., Martinez-Lopez J; Hematology Department, Hospital 12 de Octubre, i+12, CNIO, Complutense University, Madrid, Spain., Carlson JM; Microsoft Research, Redmond, WA, USA., Robins HS; Adaptive Biotechnologies, Seattle, WA, USA.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2020 Sep 17. Date of Electronic Publication: 2020 Sep 17.
DOI: 10.1101/2020.07.31.20165647
Abstrakt: 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.
Databáze: MEDLINE
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