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Predictions of immunogenicity reveal potent SARS-CoV-2 CD8+ T-cell epitopes

Gfeller, D.; Schmidt, J.; Croce, G.; Guillaume, P.; Bobisse, S.; Genolet, R.; Queiroz, L.; Cesbron, J.; Racle, J.; Harari, A.

2022-05-23 bioinformatics
10.1101/2022.05.23.492800 bioRxiv
Show 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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