Predictions of immunogenicity reveal potent SARS-CoV-2 CD8+ T-cell epitopes
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Abstract
The recognition of pathogen or cancer-specific epitopes by CD8 + T cells is crucial for the clearance of infections and the response to cancer immunotherapy. This process requires epitopes to be presented on class I Human Leukocyte Antigen (HLA-I) molecules and recognized by the T-Cell Receptor (TCR). Machine learning models capturing these two aspects of immune recognition are key to improve epitope predictions. Here we assembled a high-quality dataset of naturally presented HLA-I ligands and experimentally verified neo-epitopes. We then integrated these data with new algorithmic developments to improve predictions of both antigen presentation and TCR recognition. Applying our tool to SARS-CoV-2 proteins enabled us to uncover several epitopes. TCR sequencing identified a monoclonal response in effector/memory CD8 + T cells against one of these epitopes and cross-reactivity with the homologous SARS-CoV-1 peptide.
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SciScore for 10.1101/2022.05.23.492800: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources For the other three donors (Leu163, Leu158. Leu184), naive and effector/memory CD8+ T cells were isolated by Fluorescence-activated Cell Sorting (FACS) upon staining with anti-CD8 antibody (344710 BioLegend), anti-CCR7 antibody (353227 BioLegend) and anti-CD45RA antibody (304108 BioLegend) for 30 min at 4°C. Leu184suggested: Noneanti-CD8suggested: Noneanti-CCR7suggested: Noneanti-CD45RAsuggested: (BioLegend Cat# 304108, RRID:AB_314412)) fluorophore-conjugated anti-human antibodies. anti-human antibodies.suggested: NoneExperimental Models: Cell Lines Sentences Resources For TCR transfection, 1×106 Jurkat … SciScore for 10.1101/2022.05.23.492800: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources For the other three donors (Leu163, Leu158. Leu184), naive and effector/memory CD8+ T cells were isolated by Fluorescence-activated Cell Sorting (FACS) upon staining with anti-CD8 antibody (344710 BioLegend), anti-CCR7 antibody (353227 BioLegend) and anti-CD45RA antibody (304108 BioLegend) for 30 min at 4°C. Leu184suggested: Noneanti-CD8suggested: Noneanti-CCR7suggested: Noneanti-CD45RAsuggested: (BioLegend Cat# 304108, RRID:AB_314412)) fluorophore-conjugated anti-human antibodies. anti-human antibodies.suggested: NoneExperimental Models: Cell Lines Sentences Resources For TCR transfection, 1×106 Jurkat cells were co-electroporated with 3 μg of each TCR chain using a Neon Transfection System 100μl kit (Thermo Fisher Scientific) with the following parameters: 1325V, 10ms, 3 pulses. Jurkatsuggested: NoneResults from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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