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

• Published in: European journal of immunology 2001-06, Vol.31 (6), p.1837-1846
• Main Authors: Texier, Catherine, Pouvelle‐Moratille, Sandra, Busson, Marc, Charron, Dominique, Ménez, André, Maillère, Bernard
• Format: Article
• Language: English
• Subjects: Alleles; Allergy; Amino Acid Sequence; Bee venom; Bee Venoms - immunology; Binding assay; Computer Simulation; histocompatibility antigen HLA; HLA-DR Antigens - chemistry; HLA-DR Antigens - genetics; HLA-DR Antigens - immunology; HLA-DRB1 Chains; HLA-DRB3 Chains; HLA-DRB4 Chains; HLA-DRB5 Chains; HLA‐DR; Humans; Hymenoptera; Models, Molecular; Molecular Sequence Data; Peptide; Peptides - immunology; Phospholipases A - immunology; Protein Structure, Secondary
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200106)31:6<1837::AID-IMMU1837>3.0.CO;2-H

The second HLA‐DR molecules, which are encoded by loci different from HLA‐DRB1 are weakly polymorphic. Predominant alleles such as HLA‐DRB3*0101, HLA‐DRB4*0101 and HLA‐DRB5*0101 are therefore interesting targets to define antigenic peptides with major impact for the entire population. Strikingly, they have been poorly investigated. Thus we have characterized peptides from the major bee venom allergen that bind efficiently to these molecules and compared them to peptides specific for preponderant HLA‐DRB1 molecules. Interestingly, DRB5*0101 and DRB1*0701 molecules share four bindingpeptides and use some identical anchor residues. Similarities are also found between DRB3*0101 and its haplotype‐associated molecules DRB1*0301 and DRB1*1301. In sharp contrast, DRB4*0101 exhibits a unique binding specificity, which results from particular structural features of its peptide binding site. Yβ81 seems to alter the amino acid preferences of the P1 pocket, while Rβ71, Eβ74, Nβ26 and Cβ13 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 haplotype HLA‐DR52 exhibits peptide binding redundancies. Finally our results document functional similarities among HLA‐DR molecules and allow us to propose peptide sequences that might be useful for bee venom immunotherapy.