Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses

Kathrin Balz,Abhinav Kaushik,Franz Cemic,Chrysanthi Skevaki,Kari Nadeau,Meng Chen,Vanessa Heger,Harald Renz

doi:10.1038/s41598-021-84320-8

Abstract

The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.

Highlights

Abbreviations ACE2 Angiotensin converting enzyme 2 acute respiratory distress syndrome (ARDS) Acute respiratory distress syndrome BLAST Basic local alignment search tool HLA Human leukocyte antigen IEDB Immune epitope database MHC Major histocompatibility complex NCBI National Center for Biotechnology Information RNA Ribonucleic acid +ssRNA Positive-sense single-stranded RNA Th 1 T-helper 1 Th 2 T-helper 2
These preliminary clinical and laboratory observations along with our prior experimental evidence involving RNA viruses led us hypothesize that SARS-CoV-2 may share a degree of protein sequence homology to allergens, which may lead to the generation of cross-reactive T cell epitopes
In order to examine our working hypothesis, we applied two distinct independent, complementary and systematic bioinformatics approaches (Fig. 1): (a) Pipeline 1-prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and a comprehensive set of allergen protein sequences combined with alignment strategies and ranking of results based on clinical and sequence conservation criteria and (b) Pipeline 2- alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell e pitopes[13]

Summary

Introduction

Abbreviations ACE2 Angiotensin converting enzyme 2 ARDS Acute respiratory distress syndrome BLAST Basic local alignment search tool HLA Human leukocyte antigen IEDB Immune epitope database MHC Major histocompatibility complex NCBI National Center for Biotechnology Information RNA Ribonucleic acid +ssRNA Positive-sense single-stranded RNA Th 1 T-helper 1 Th 2 T-helper 2. Other investigators reported that T cells in peripheral blood of COVID-19 patients with allergy were increased as compared to patients without a llergies[12] These preliminary clinical and laboratory observations along with our prior experimental evidence involving RNA viruses led us hypothesize that SARS-CoV-2 may share a degree of protein sequence homology to allergens, which may lead to the generation of cross-reactive T cell epitopes. Pre-existing T cells specific for such cross-reactive allergenderived epitopes may have an impact on COVID-19 outcome via aberrant cytokine responses to the virus peptides These cytokines could prevent an overshooting T1 inflammatory reaction, both locally (as in the case of preexisting pulmonary C D4+ T cells specific to inhalant allergens) and/or systemically. We sought to predict potentially cross-reactive allergen- and SARS-CoV-2-derived MHC Class I and Class II T cell epitopes, which can be presented by the most prevalent HLA alleles

Methods

Conclusion