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- W3091852667 abstract "Introduction: Delineating antiviral T-cell responses to SARS-CoV-2 may shed light on the heterogeneity of clinicaloutcomes and inform vaccine or therapeutic approaches Viral antigens can be predicted using computational toolsthat calculate the binding affinity between viral peptides and antigen presentation machinery However, in order toaccount for the role of host genetics in the diversity of responses, this analysis must be performed withconsideration of the global diversity of the human leukocyte antigen (HLA) proteins responsible for antigenpresentation Methods: We deployed binding predictions across the SARS-CoV-2 peptidome for 9,360 Class I HLA alleles (2,987HLA-A;3,707 HLA-B;2,666 HLA-C;9-mers) using a consensus approach of 7 algorithms and 3,486 Class II HLAalleles (15-mers) using a consensus approach of 4 algorithms All pMHC predictions were filtered to include onlythose with consensus binding less than 500 nM Results: There were 368,145 unique combinations of peptides and HLA alleles (pMHCs) with a predicted bindingaffinity of less than 500nM, including 1,103 unique 9-mer and 2,547 15-mer peptides and 1,022 MHC Class I and8,075 MHC Class II HLA proteins Of these pMHCs, 82% of 9-mers overlapped with 15-mers, suggesting cross-presentation to both CD4 and CD8 T cells in a subset of individuals We evaluated this filtered dataset with respectto the population frequency of HLA haplotypes While the predicted susceptibility of SARS-CoV-2 antigenpresentation differed greatly across countries, there was a subset of 21 Class I antigens shared by common HLAtypes across 30 or more countries (out of 79 countries with reported population frequency data) Our database hasbeen made publicly available, and we have developed a user interface to explore the results based upon viralproteins, HLA alleles, or country populations of interest Conclusions: With the ongoing SARS-CoV-2 pandemic, there are worldwide efforts to generate a successfulvaccine and to evaluate clinical samples to understand the viral pathogenesis and diverse outcomes in patients This application can serve as a guide to identify responses of putative SARS-CoV-2-specific T cells across patients with a broad range of HLA haplotypes internationally" @default.
- W3091852667 created "2020-10-15" @default.
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- W3091852667 date "2020-01-01" @default.
- W3091852667 modified "2023-09-26" @default.
- W3091852667 title "Pan-HLA prediction of SARS-CoV-2 epitopes" @default.
- W3091852667 hasPublicationYear "2020" @default.
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