Journal
BIOLOGY METHODS & PROTOCOLS
Volume 8, Issue 1, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/biomethods/bpad011
Keywords
T cells; immunogenic epitopes; epitopes; peptide vocabulary; COVID; SARS-CoV-2; origin
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Computational prediction of T cell epitopes is crucial for vaccine development. Using Monte Carlo tests, we found that T cell-stimulating peptides have a significantly higher proportion of pentapeptides, hexapeptides, and heptapeptides not found in the human proteome. Our novel method for predicting T cell immunogenicity of SARS-CoV-2 peptides is four times more effective than previous approaches.
Computational prediction of T cell epitopes is a crucial component in the development of novel vaccines. T cells in a healthy vertebrate host can recognize as non-self only those peptides that are present in the parasite's proteins but absent in the host's proteins. This principle enables us to determine the current and past host specificity of a parasite and to predict peptides capable of eliciting a T cell response. Building upon the detailed mapping of T cell clone specificity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigens, we employed Monte Carlo tests to determine that empirically confirmed T cell-stimulating peptides have a significantly increased proportion of pentapeptides, hexapeptides and heptapeptides not found in the human proteome (P < 0.0001, Cohen's d > 4.9). We observed a lower density of potential pentapeptide targets for T cell recognition in the spike protein from the human-adapted SARS-CoV-2 ancestor compared to 10 other SARS-CoV-2 proteins originating from the horseshoe bat-adapted ancestor. Our novel method for predicting T cell immunogenicity of SARS-CoV-2 peptides is four times more effective than previous approaches. We recommend utilizing our theory-based method where efficient empirically based algorithms are unavailable, such as in the development of certain veterinary vaccines, and combining it with empirical methods in other cases for optimal results.
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