HLA-DR restricted peptide candidates for bee venom immunotherapy

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