THE ROLE OF HLA-DP-BETA RESIDUE-69 IN THE DEFINITION OF ANTIBODY-BINDING EPITOPES

Residue 69 of the DP beta chain has been previously identified as bein g involved in T-cell recognition as well as in the susceptibility to c ertain autoimmune diseases, The codon for Glu 69 in the DPB1()02012 a llele was changed to the codon for Lys found in DPB1()0402, and trans fectant L cells expressing wild-type or mutant HLA-DP molecule were ob tained. The binding of a large panel of mAbs to these transfectants wa s tested by flow cytometry. Glu to Lys 69 substitution decreased the b inding to the DPB1()02012 allele of some of the DP mAbs and completel y eliminated the binding of four of the antibodies tested. These resul ts clearly showed that this residue is involved in the formation of DP antibody-binding epitopes. Because this residue should be located in the alpha-helix of the DP beta polypeptide with the side chain pointin g into the peptide-binding groove, its implication in the definition i n some DP antibody-binding epitopes should be (a) defining conformatio nal epitopes through effects on the conformation of adjacent regions o f the molecule, and (b) determining the binding of peptides to the DP cleft which is directly or indirectly involved in these epitopes.