The presenting HLA determines fidelity of SARS-CoV-2 spike protein epitope prediction

Abstract

During the course of the COVID-19 pandemic, multiple studies used prediction methods to identify potential epitopes. While additional studies identified epitopes from convalescent and vaccinated subjects, few studies have compared the predicted to identified epitopes. Here we used three methods alone and in combination to predict helper T cell epitopes and compared the results to experimentally determined peptide binding. The correspondence between the results predicted from each method or combination and experimental results depends on the HLA being investigated. We were also able identify the prediction methods which lead to the most consistent results. Lastly, these observations were extended to more HLAs to predict epitopes which may be globally presented. All the predicted epitopes were previously identified as helper T cell epitopes. These results suggest predicting the binding to a larger number of HLAs may lead to higher fidelity identification of epitopes.