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

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.

背景：目前学界对人类白细胞抗原（human leukocyte antigens, HLAs）与食物过敏之间的关联所知甚少。本研究旨在通过生物信息学手段分析人类白细胞抗原II类基因多态性与食物过敏的关联。
方法：本研究开发了一种模拟人体食物过敏原加工过程的两步算法。第一步，过敏原经胃蛋白酶、胰蛋白酶及胰凝乳蛋白酶消化降解；第二步，将消化得到的肽段与人群中最常见的12种HLA-DRB1等位基因及5种HLA-DQ等位基因进行结合，并预测其结合亲和力。
结果：本研究将该算法应用于13种常见的牛乳及鸡蛋过敏原。将预测得到的HLA结合肽段与上述过敏原已知的T细胞表位及IgE表位进行比对，发现其中77%的肽段与表位存在重叠。研究发现，牛乳过敏原衍生肽段可与DRB1*01:01、DQ7及DQ8结合，而无法与DRB1*03:01、DRB1*04:04、DRB1*12:01及DRB1*15:01结合。鸡蛋过敏原衍生肽段可与DRB1*01:01、DQ4、DQ7及DQ8结合，而无法与DRB1*03:01、DRB1*04:04及DRB1*12:01结合；所有受试HLA-DQ等位基因均可与鸡蛋过敏原肽段结合。可将能与过敏原肽段结合的等位基因视为对应食物过敏的易感等位基因，无法结合的等位基因则为保护等位基因。
结论：DRB1*01:01、DQ7及DQ8等位基因可视为牛乳过敏的易感等位基因，DRB1*03:01、DRB1*04:04、DRB1*12:01及DRB1*15:01则为其保护等位基因。DRB1*01:01、DQ4、DQ7及DQ8等位基因可视为鸡蛋过敏的易感等位基因，DRB1*03:01、DRB1*04:04及DRB1*12:01则为其保护等位基因；本研究未发现针对鸡蛋过敏的保护性HLA-DQ等位基因。