Associations between Milk and Egg Allergens and the HLA-DRB1/DQ Polymorphism: A Bioinformatics Approach

Abstract

Background: Little is known about the associations between human leukocyte antigens (HLAs) and food allergies. Our aim was to analyze the associations between the HLA class II polymorphism and food allergy using bioinformatics. Methods: A two-step algorithm was developed which mimics the food allergen processing in the human body. In the first step, the allergen is digested by pepsin, trypsin and chymotrypsin. In the second step, the digested fragments bind to the most frequent 12 HLA-DRB1 and 5 HLA-DQ alleles, and the binding affinities are predicted. Results: The algorithm was applied to 13 well-known milk and egg allergens. The predicted HLA binders were compared to known T-cell and IgE epitopes originating from the same allergens, and 77% of them were found to overlap. We found that the peptides generated from milk allergens bind to DRB1*01:01, DQ7 and DQ8 but not to DRB1*03:01, DRB1*04:04, DRB1*12:01 and DRB1*15:01. The peptides generated from egg allergens bind to DRB1*01:01, DQ4, DQ7 and DQ8 but not to DRB1*03:01, DRB1*04:04 and DRB1*12:01. They bind to all the DQs studied. The alleles that bind to allergen peptides could be considered as susceptible to the particular allergy and the nonbinding alleles as protective. Conclusions: The alleles DRB1*01:01, DQ7 and DQ8 are considered as susceptible to cow's milk allergy and DRB1*03:01, DRB1*04:04, DRB1*12:01 and DRB1*15:01 as protective. The alleles DRB1*01:01, DQ4, DQ7 and DQ8 are considered as susceptible to egg allergy and DRB1*03:01, DRB1*04:04 and DRB1*12:01 as protective. Protective DQs against egg allergy were not revealed in this study.

HLA Polymorphisms and Food Allergy Predisposition

“…This study failed to reveal any protective DQs against egg allergy. 20 Based on these findings, it can be assumed that HLA class II and many of respective haplotypes, such as the above-mentioned DQ and DR interact with the IgE epitopes and they both have an important impact on the development of FA.…”

“…Moreover, the peptides that derived from egg allergens bind also to DQ4 (DQA1 Ã 04: 01/DQB1 Ã 04: 02). 20 Notwithstanding, egg was examined in two GWAS about its correlation with HLA alleles. The researchers found no association between this food allergen and the HLA alleles.…”

Recent Advances in Clinical Allergy and Immunology

“…In order to study the association between milk and egg allergies and HLA polymorphisms, a bioinformatics approach was applied that mimicked the enzymatic degradation of food allergens and evaluated their binding affinity to DR and/or DQ molecules. Three susceptibility loci for milk and four for egg allergies, as well as four protective alleles for milk allergy, were identified [39]. …”

Navigating through the Jungle of Allergens: Features and Applications of Allergen Databases

“…First, the most basic application of Allergome is retrieving a comprehensive list of known allergens from a specific source. Dimitrov and Doytchinova [13] used Allergome to retrieve the sequences of 13 milk and egg allergens in order to simulate their gastrointestinal digestion and peptide-HLA-binding. They predicted 3 and 4 HLA-DR and DQ alleles binding to peptides from milk and egg allergens, respectively, while several alleles did not bind to allergen-derived peptides and were hence considered to be protective against the respective allergies.…”