Xinrong Guo

Stanford University

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Gan Zhao

Children's Hospital of Philadelphia

Jiawang Hou

Biomedical Research Institute

Alex Cheng

Vanderbilt University Medical Center

Sheng Jiang

Fudan University

Yuan Ding

Hohai University

Shuting Wu

Southern Medical University

Zhiyu Zhang

Shanghai Changzheng Hospital

Yue He

Affiliated Hospital of Southwest Medical University

Bin Wang

Fudan University

Bing Su

Shanghai Jiao Tong University

Cooperative Institutions

Shanghai Jiao Tong University

Stanford University

Fudan University

Chinese Academy of Medical Sciences & Peking Union Medical College

State Key Laboratory of Oncogene and Related Genes

Biomedical Research Institute

Ruijin Hospital

National Institutes of Health

Shanghai Public Health Clinical Center

Qingdao University

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Dynamics of TCR repertoire and T cell function in COVID-19 convalescent individuals

Cell Discovery (2021)

Lingjie Luo Wenhua Liang Jianfeng Pang Gang Xu Yingying Chen

Abstract SARS-CoV-2 outbreak has been declared by World Health Organization as a worldwide pandemic. However, there are many unknowns about the antigen-specific T-cell-mediated immune responses to SARS-CoV-2 infection. Here, we present both single-cell TCR-seq and RNA-seq to analyze the dynamics of TCR repertoire and immune metabolic functions of blood T cells collected from recently discharged COVID-19 patients. We found that while the diversity of TCR repertoire was increased in discharged patients, it returned to basal level ~1 week after becoming virus-free. The dynamics of T cell repertoire correlated with a profound shift of gene signatures from antiviral response to metabolism adaptation. We also demonstrated that the top expanded T cell clones (~10% of total T cells) display the key anti-viral features in CD8 + T cells, confirming a critical role of antigen-specific T cells in fighting against SARS-CoV-2. Our work provides a basis for further analysis of adaptive immunity in COVID-19 patients, and also has implications in developing a T-cell-based vaccine for SARS-CoV-2.

10.1038/s41421-021-00321-x

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Citations (38)

Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Sheng Jiang Shuting Wu Gan Zhao Yue He Xinrong Guo

ABSTRACT The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants including the most recent Omicron and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

CTL*

ELISPOT

Epitope mapping

10.1101/2021.11.21.469172

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Citations (2)

Identification of a Promiscuous Conserved CTL Epitope Within the SARS-CoV-2 Spike Protein

Research Square (Research Square) (2021)

Sheng Jiang Shuting Wu Gan Zhao Yue He Xinrong Guo

Abstract The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC‑I and MHC‑II epitopes by ELIspot and cytolytic assays to a conserved MHC‑I epitope. The epitope is highly conserved in current viral variants and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

CTL*

ELISPOT

10.21203/rs.3.rs-936389/v1

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Citations (0)

Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein

Emerging Microbes & Infections (2022)

Sheng Jiang Shuting Wu Gan Zhao Yue He Xinrong Guo

ABSTRACTThe COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development, and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus-neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. This study predicted several potential T cell epitopes with web-based analytic tools and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants and compatible with a presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

CTL*

ELISPOT

Epitope mapping

10.1080/22221751.2022.2043727

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Citations (12)

Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease

Immunity (2024)

Saborni Chakraborty Bowie Yik-Ling Cheng Desmond L. Edwards Joseph C. González David Kung‐Chun Chiu

While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung inflammation and protecting lung function during influenza infection. Therapeutic administration of a recombinant, sialylated Fc molecule in clinical development similarly activated REST and protected against severe influenza disease, demonstrating that this pathway could be clinically harnessed. Overall, induction of REST through sialylated IgG signaling is a strategy to limit inflammatory disease sequelae in infections caused by antigenically distinct influenza strains.

Rest (music)

Alveolar macrophage

10.1016/j.immuni.2024.10.002

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Citations (3)