Complementarity and redundancy of the binding specificity of HLA-DRB1,-DRB3,-DRB4 and-DRB5 molecules

The second HLA-DR molecules, which are encoded by loci different from HLA-D RB1 are weakly polymorphic. Predominant alleles such as HLA-DRB3*0101, HLA- DRB4*0101 and HLA-DRB5*0101 are therefore interesting targets to define ant igenic peptides with major impact for the entire population. Strikingly, th ey have been poorly investigated. Thus we have characterized peptides from the major bee venom allergen that bind efficiently to these molecules and c ompared them to peptides specific for preponderant HLA-DRB1 molecules. Inte restingly, DRB5*0101 and DRB1*0701 molecules share four binding peptides an d use some identical anchor residues. Similarities are also found between D RB3*0101 and its haplotype-associated molecules DRB1*0301 and DRB1*1301. In sharp contrast, DPR4*0101 exhibits a unique binding specificity, which res ults from particular structural features of its peptide binding site. Y bet a 81 seems to alter the amino acid preferences of the P1 pocket, while R be ta 71, E beta 74, N beta 26 and C beta 13 confer to the P4 pocket a unique topology. Our results show that the two HLA-DR molecules expressed in most haplotypes studied here have mostly complementary binding patterns. Only ha plotype HLA-DR52 exhibits peptide binding redundancies. Finally our results document functional similarities among HLA-DR molecules and allow us to pr opose peptide sequences that might be useful for bee venom immunotherapy.