HLA-DRα chain residues located on the outer loops are involved in nonpolymorphic and polymorphic antibody-binding epitopes

• Published in: Human immunology Vol. 39; no. 4; pp. 253 - 260
• Main Authors: Fu, Xin-Ting, Karr, Robert W.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.1994; Elsevier Science
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal - immunology; Antigens; Binding Sites, Antibody - immunology; Biological and medical sciences; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocompatibility antigens (hla, h-2 and other systems); HLA-DR Antigens - chemistry; HLA-DR Antigens - immunology; Humans; Molecular immunology; Molecular Sequence Data; Mutagenesis, Site-Directed; Polymerase Chain Reaction; Protein Conformation; Structure-Activity Relationship; Transfection; Human; Antigen presentation; HLA-System; Antigenicity; Antigenic determinant; Major histocompatibility system; Class II histocompatibility antigen; Alpha-Peptide chain; HLA-DR-Locus; Structure function relationship
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/0198-8859(94)90268-2

The structure-function relationships of the HLA-DRα chain have been analyzed by identifying DRα residues involved in several nonpolymorphic and polymorphic antibody epitopes. Antibody binding to transfectants expressing a WT or mutant DRα chain with the WT DR (β1 ∗0701) chain was analyzed. Our results indicate that residues 18, 36, and 39 located on the outer loops of the DRα chain are critical for one of more of the epitopes recognized by the SG157, Q2/70, L243, LB3. 1, D1-12, and CL413 mAbs. Similar results were obtained when the DRα position 18 and 39 mutants were expressed with other DRβ1 allesles. Furthermore, residues 15 and 18 of the DRα chain were shown to be involved in the epitopes of two polymorphic mAbs, HU-26 and I-2, whose epitopes also include residue 4 of the corresponding DRβ chains. In addition to their involvement in antibody-binding epitopes, residues in this region on the outer surface of the DRα chain have also been shown to be involved in superantigen binding and presentation and T-cell recognition of foreign antigen, emphasizing the functional importance of DRα-chain residues located outside of the peptide-binding groove.