Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T-cell memory formation after mild COVID-19 infection

COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T...

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Published in:	eLife Vol. 10
Main Authors:	Minervina, Anastasia A, Komech, Ekaterina A, Titov, Aleksei, Bensouda Koraichi, Meriem, Rosati, Elisa, Mamedov, Ilgar Z, Franke, Andre, Efimov, Grigory A, Chudakov, Dmitriy M, Mora, Thierry, Walczak, Aleksandra M, Lebedev, Yuri B, Pogorelyy, Mikhail V
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 05.01.2021 eLife Sciences Publications Ltd eLife Sciences Publication eLife Sciences Publications, Ltd
Subjects:	Amino Acid Sequence Antibodies Antigens Antiviral agents Antiviral drugs B cells CD4 antigen CD8 antigen Cloning Computational and Systems Biology Coronaviruses COVID-19 COVID-19 - immunology COVID-19 - physiopathology COVID-19 vaccines Cross Reactions Cross-reactivity Epidemics Epitope Mapping Female Fever Gene Library Genotype & phenotype Health aspects Histocompatibility Testing Humans Immune response Immunologic Memory Immunological memory Immunology and Inflammation Infection Infections Life Sciences Longitudinal Studies Lymphocytes Lymphocytes T Male Memory cells Pandemics Peptides Phenotypes Receptors, Antigen, T-Cell - chemistry Receptors, Antigen, T-Cell - genetics RepSeq SARS-CoV-2 SARS-CoV-2 - physiology Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Short Report T cell receptors T cells T-Lymphocytes - immunology TCR Viral antibodies Viral infections COVID-19 computational biology systems biology RepSeq SARS-CoV-2 TCR inflammation human immunology
ISSN:	2050-084X, 2050-084X
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Abstract	COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4 + and CD8 + T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.
AbstractList	COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4 + and CD8 + T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2. COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4 and CD8 T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2. COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4+ and CD8+ T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2. COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4+ and CD8+ T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4+ and CD8+ T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2. COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4.sup.+ and CD8.sup.+ T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.
Audience	Academic
Author	Mamedov, Ilgar Z Rosati, Elisa Chudakov, Dmitriy M Franke, Andre Walczak, Aleksandra M Minervina, Anastasia A Efimov, Grigory A Pogorelyy, Mikhail V Mora, Thierry Komech, Ekaterina A Titov, Aleksei Bensouda Koraichi, Meriem Lebedev, Yuri B
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Copyright	2021, Minervina et al. COPYRIGHT 2021 eLife Science Publications, Ltd. 2021, Minervina et al. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Attribution 2021, Minervina et al 2021 Minervina et al
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Keywords	COVID-19 computational biology systems biology RepSeq SARS-CoV-2 TCR inflammation human immunology
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SubjectTerms	Amino Acid Sequence Antibodies Antigens Antiviral agents Antiviral drugs B cells CD4 antigen CD8 antigen Cloning Computational and Systems Biology Coronaviruses COVID-19 COVID-19 - immunology COVID-19 - physiopathology COVID-19 vaccines Cross Reactions Cross-reactivity Epidemics Epitope Mapping Female Fever Gene Library Genotype & phenotype Health aspects Histocompatibility Testing Humans Immune response Immunologic Memory Immunological memory Immunology and Inflammation Infection Infections Life Sciences Longitudinal Studies Lymphocytes Lymphocytes T Male Memory cells Pandemics Peptides Phenotypes Receptors, Antigen, T-Cell - chemistry Receptors, Antigen, T-Cell - genetics RepSeq SARS-CoV-2 SARS-CoV-2 - physiology Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Short Report T cell receptors T cells T-Lymphocytes - immunology TCR Viral antibodies Viral infections
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Title	Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T-cell memory formation after mild COVID-19 infection
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