Cross-reactive MHC Class I T Cell Epitopes May Dictate Heterologous Immune Responses Between Respiratory Viruses and Food Allergens

Respiratory virus infections play a major role in asthma inception, persistence, and exacerbations. There is also a close correlation between asthma and food allergy, and we hypothesize that food-allergen-induced T cell-mediated heterologous immunity likely plays a role in inducing asthma symptoms in sensitized individuals. In this study, we used two independent in silico pipelines for the identification of cross-reactive virus- and food allergen- derived T cell epitopes, considering individual peptide sequence similarity, MHC binding affinity and immunogenicity. We assessed the proteomes of human rhinovirus (RV1b), respiratory syncytial virus (RSVA2) and influenza-strains contained in the seasonal quadrivalent influenza vaccine 2019/2020 (QIV 2019/2020), as well as SARS-CoV-2 for the most frequent human HLA alleles, in addition to more than 200 most common food allergen protein sequences. All resulting allergen-derived peptide candidates were subjected to an elaborate scoring system considering multiple criteria, including clinical relevance. In both bioinformatics approaches, we found that shortlisted peptide pairs that are potentially binding to MHC class II molecules scored up to 10x lower compared to MHC class I candidate epitopes. For MHC class I food allergen epitopes, several candidate peptides from shrimp, kiwi, apple, soy bean and chicken were identified. Such allergen sources contained potentially cross-reactive epitopes to the aforementioned viruses. The shortlisted set of peptide pairs may be implicated as heterologous virus-mediated immune response to food allergens. Our findings may be translated to peptide immunization strategies with immunomodulatory properties.