Cross-reactive and mono-reactive SARS-CoV-2 CD4+ T cells in prepandemic and COVID-19 convalescent individuals
| Autor: | Alexandra M. Johansson, William W. Kwok, Maxwell P. Krist, David M. Koelle, Uma Malhotra, Anna Wald, Yeseul G. Kim, Rebecca Gomez |
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| Rok vydání: | 2021 |
| Předmět: |
RNA viruses
CD4-Positive T-Lymphocytes Viral Diseases Coronaviruses viruses Epitopes T-Lymphocyte Protein Sequencing Biochemistry Epitope White Blood Cells Epitopes Medical Conditions Animal Cells Medicine and Health Sciences Biology (General) Peptide sequence Pathology and laboratory medicine Cross Reactivity Staining T Cells Cell Staining Medical microbiology Phenotype Infectious Diseases medicine.anatomical_structure Viruses Spike Glycoprotein Coronavirus Structural Proteins Cellular Types SARS CoV 2 Pathogens Research Article Subdominant SARS coronavirus QH301-705.5 Immune Cells Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cell Immunology Cross Reactions Biology Research and Analysis Methods Microbiology Virology Homologous chromosome medicine Genetics Humans Molecular Biology Techniques Sequencing Techniques Pandemics Molecular Biology Blood Cells SARS-CoV-2 Gene Mapping Organisms Viral pathogens Biology and Life Sciences Proteins COVID-19 Covid 19 Convalescence Cell Biology RC581-607 Microbial pathogens Specimen Preparation and Treatment Parasitology Immunologic diseases. Allergy Epitope Mapping Ex vivo |
| Zdroj: | PLoS Pathogens, Vol 17, Iss 12, p e1010203 (2021) PLoS Pathogens |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1010203 |
| Popis: | Class II tetramer reagents for eleven common DR alleles and a DP allele prevalent in the world population were used to identify SARS-CoV-2 CD4+ T cell epitopes. A total of 112, 28 and 42 epitopes specific for Spike, Membrane and Nucleocapsid, respectively, with defined HLA-restriction were identified. Direct ex vivo staining of PBMC with tetramer reagents was used to define immunodominant and subdominant T cell epitopes and estimate the frequencies of these T cells in SARS-CoV-2 exposed and naïve individuals. Majority of SARS-CoV-2 epitopes identified have Author summary Previous studies with activation induced marker assays in monitoring antigen-specific CD4+ T cells have shown that common cold coronavirus T cells can cross-react with SARS-CoV-2 antigens and these cross-reactive T cells are present in up to 60% of the unexposed population. In this current study, sets of overlapping peptides for Spike, Membrane, and Nucleocapsid proteins were used to identify epitopes across 11 HLA-DR and 1 HLA-DP alleles in SARS-CoV-2 convalescent samples using peptide-loaded MHC-II tetramers. Using these tetramers ex vivo, frequencies of these epitope-specific T cells were estimated in convalescent and pre-pandemic samples. Based on these frequencies, epitopes were stratified into immunodominant and subdominant epitopes. Amino acid sequences of epitopes identified were compared with 4 common cold coronaviruses. Potential cross-reactive epitopes were defined as having ≥67% sequence identity between common cold viruses and SARS-CoV-2. Four potential Spike specific cross-reactive epitopes were identified and functional cross-reactivity was demonstrated. Of the four cross-reactive epitopes identified, three were subdominant epitopes eliciting relatively low frequencies in both unexposed and convalescent subjects. In contrast to the results from the activation induced marker assays, the current data suggests that only a limited number of high avidity SARS-CoV-2 T cells as detected by tetramers are cross-reactive. |
| Databáze: | OpenAIRE |
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