HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy

TLDR

T cell epitope peptides are proposed as better‑tolerated alternatives to conventional allergen extracts, but their clinical use is limited by HLA‑II polymorphism, with seven DRB1 alleles dominating in Caucasians. The study aims to identify bee venom peptides that efficiently bind these prevalent HLA‑DR alleles for potential immunotherapy. Synthetic peptides covering the entire major bee venom allergen were tested for binding to each of the seven DRB1 alleles. Multiple peptides were found to bind efficiently, including a universal 81–97 sequence that binds all seven alleles and a 76–106 region rich in determinants, with statistical analysis highlighting allele‑specific binding patterns.

Abstract

Abstract T cell epitopes containing peptides have been recently proposed as an alternative to conventional immunotherapy of allergic diseases because they are expected to be better tolerated than allergen extracts. A principal limitation to their clinical use is that they present an important diversity, which primarily results from the polymorphism of HLA class II molecules. In Caucasian populations, however, seven alleles of the most expressed molecules (namely DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301, and DRB1*1501) predominate. Peptides from allergens that would efficiently bind to them should be potential candidates for specific immunotherapy. In this paper, we have determined the peptides present in the major bee venom allergen by investigating the capacity of synthetic peptides that encompass its whole sequence to bind to each allele. Several efficient binders have been identified and are either allele-specific or common to several HLA-DR molecules. Interestingly enough, the 81–97 sequence is universal in the sense that it binds to all studied molecules. This sequence is surrounded by several active regions, which make the 76–106 sequence particularly rich of binding determinants and a good candidate for specific immunotherapy. Statistical analyses of the binding data also provide an overview of the preponderant HLA-DR alleles specificity.