Multiple regions of HLA-DR beta 1 chains determine polymorphic epitopes recognized by monoclonal antibodies.
To investigate the locations of antibody binding epitopes on HLA class II molecules, four DR4/7 beta 1 hybrid cDNA were constructed by exchanging the DNA encoding the NH2-terminal portions (amino acids 1 to 40) or the COOH-terminal portions (amino acids 41 to 94) of the first domains of DR4 beta 1- and DR7 beta 1-chains, in association with DNA encoding either the DR4 beta 1 or DR7 beta 1 second domains. Transfectants expressing a DR alpha cDNA and a wild-type DR4 beta 1 or DR7 beta 1 cDNA or one of four hybrid DR4/7 beta 1 cDNA were produced, and the binding to the transfectants of anticlass II mAb, which detect polymorphic epitopes on either DR4 or DR7 molecules, was analyzed. Four different patterns of mAb binding to the transfectants were observed, indicating that multiple regions of DR beta 1-chains play the predominant roles in the contributions of these chains to polymorphic epitopes recognized by mAb on intact molecules. The relevant regions of these chains and the number of mAb that recognize the associated polymorphic epitopes are: 1) the COOH-terminal portion of the first domain of DR4 beta 1; a DR4-specific mAb, 2) the NH2-terminal portion of the first domain of DR7 beta 1; two mAb, including a DR7-specific mAb, 3) the NH2-terminal portion of the first domain of DR4 beta 1; seven mAb, and 4) the second domain of DR4 beta 1; one mAb.
Alber
C A
CA
Veterans Administration Medical Center, Iowa City 52246.
Watts
R
R
Klohe
E P
EP
Drover
S
S
Marshall
W H
WH
Radka
S F
SF
Karr
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000378:metabolism; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007739:L Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D011110:Polymorphism, Genetic; D051381:Rats; D011917:Rats, Inbred Lew; D014162:Transfection
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006684:HLA-DR Antigens