title: HLA-DR alpha chain residues located on the outer loops are involved in nonpolymorphic and polymorphic antibody-binding epitopes.
abstract: The structure-function relationships of the HLA-DR alpha chain have been analyzed by identifying DR alpha residues involved in several nonpolymorphic and polymorphic antibody epitopes. Antibody binding to transfectants expressing a WT or mutant DR alpha chain with the WT DR(beta 1*0701) chain was analyzed. Our results indicate that residues 18, 36, and 39 located on the outer loops of the DR alpha chain are critical for one or more of the epitopes recognized by the SG157, Q2/70, L243, LB3.1, D1-12, and CL413 mAbs. Similar results were obtained when the DR alpha position 18 and 39 mutants were expressed with other DR beta 1 alleles. Furthermore, residues 15 and 18 of the DR alpha 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 DR beta chains. In addition to their involvement in antibody-binding epitopes, residues in this region on the outer surface of the DR alpha 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 DR alpha-chain residues located outside of the peptide-binding groove.
authors.affiliation: Department of Immunology and Infectious Diseases, Monsanto Company, St. Louis, Missouri 63198.
authors.forename: X T
authors.initials: XT
authors.lastname: Fu
authors.forename: R W
authors.initials: RW
authors.lastname: Karr
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006684:HLA-DR Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D006684:HLA-DR Antigens