The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells
Abstract Severe COVID-19 can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) with similarities to superantigen-induced toxic shock syndrome. An outstanding question is whether SARS-CoV-2 protein sequences can directly induce inflammatory responses. In this study, we i...
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07350-8 |
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| author | Thai Hien Tu Fatima Ezzahra Bennani Nasser Masroori Chen Liu Atena Nemati Nicholas Rozza Amichai Meir Grunbaum Richard Kremer Catalin Milhalcioiu Denis-Claude Roy Christopher E. Rudd |
| author_facet | Thai Hien Tu Fatima Ezzahra Bennani Nasser Masroori Chen Liu Atena Nemati Nicholas Rozza Amichai Meir Grunbaum Richard Kremer Catalin Milhalcioiu Denis-Claude Roy Christopher E. Rudd |
| author_sort | Thai Hien Tu |
| collection | DOAJ |
| description | Abstract Severe COVID-19 can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) with similarities to superantigen-induced toxic shock syndrome. An outstanding question is whether SARS-CoV-2 protein sequences can directly induce inflammatory responses. In this study, we identify a region in the SARS-CoV-2 S2 spike protein with sequence homology to bacterial super-antigens (termed P3). Computational modeling predicts P3 binding to sites on MHC class I/II and the TCR that partially overlap with sites for the binding of staphylococcal enterotoxins B and H. Like SEB and SEH derived peptides, P3 stimulated 25–40% of human CD4+ and CD8 + T-cells, increasing IFN-γ and granzyme B production. viSNE and SPADE profiling identified overlapping and distinct IFN-γ+ and GZMB+ subsets. The super-antigenic properties of P3 were further evident by its selective expansion of T-cells expressing specific TCR Vα and Vβ chain repertoires. In vivo experiments in mice revealed that the administration of P3 led to a significant upregulation of proinflammatory cytokines IL-1β, IL-6, and TNF-α. While the clinical significance of P3 in COVID-19 remains unclear, its homology to other mammalian proteins suggests a potential role for this peptide family in human inflammation and autoimmunity. |
| format | Article |
| id | doaj-art-965db4d8d39246fa975a98e071a94bb6 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-965db4d8d39246fa975a98e071a94bb62025-01-12T12:35:53ZengNature PortfolioCommunications Biology2399-36422025-01-018111510.1038/s42003-024-07350-8The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cellsThai Hien Tu0Fatima Ezzahra Bennani1Nasser Masroori2Chen Liu3Atena Nemati4Nicholas Rozza5Amichai Meir Grunbaum6Richard Kremer7Catalin Milhalcioiu8Denis-Claude Roy9Christopher E. Rudd10Department of Medicine, Universite de MontrealDepartment of Microbiology, Infection and Immunology, Universite de MontrealDepartment of Medicine, Universite de MontrealDepartment of Medicine, Universite de MontrealDepartment of Medicine, Universite de MontrealDivision of Experimental Medicine, Department of Medicine & Health Sciences, McGill University Health Centre, McGill UniversityDivision of Experimental Medicine, Department of Medicine & Health Sciences, McGill University Health Centre, McGill UniversityDivision of Experimental Medicine, Department of Medicine & Health Sciences, McGill University Health Centre, McGill UniversityDepartment of Medicine, McGill University Health CenterDepartment of Medicine, Universite de MontrealDepartment of Medicine, Universite de MontrealAbstract Severe COVID-19 can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) with similarities to superantigen-induced toxic shock syndrome. An outstanding question is whether SARS-CoV-2 protein sequences can directly induce inflammatory responses. In this study, we identify a region in the SARS-CoV-2 S2 spike protein with sequence homology to bacterial super-antigens (termed P3). Computational modeling predicts P3 binding to sites on MHC class I/II and the TCR that partially overlap with sites for the binding of staphylococcal enterotoxins B and H. Like SEB and SEH derived peptides, P3 stimulated 25–40% of human CD4+ and CD8 + T-cells, increasing IFN-γ and granzyme B production. viSNE and SPADE profiling identified overlapping and distinct IFN-γ+ and GZMB+ subsets. The super-antigenic properties of P3 were further evident by its selective expansion of T-cells expressing specific TCR Vα and Vβ chain repertoires. In vivo experiments in mice revealed that the administration of P3 led to a significant upregulation of proinflammatory cytokines IL-1β, IL-6, and TNF-α. While the clinical significance of P3 in COVID-19 remains unclear, its homology to other mammalian proteins suggests a potential role for this peptide family in human inflammation and autoimmunity.https://doi.org/10.1038/s42003-024-07350-8 |
| spellingShingle | Thai Hien Tu Fatima Ezzahra Bennani Nasser Masroori Chen Liu Atena Nemati Nicholas Rozza Amichai Meir Grunbaum Richard Kremer Catalin Milhalcioiu Denis-Claude Roy Christopher E. Rudd The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells Communications Biology |
| title | The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells |
| title_full | The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells |
| title_fullStr | The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells |
| title_full_unstemmed | The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells |
| title_short | The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells |
| title_sort | identification of a sars cov2 s2 protein derived peptide with super antigen like stimulatory properties on t cells |
| url | https://doi.org/10.1038/s42003-024-07350-8 |
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