Mapping of the Epstein-Barr virus and C3dg binding sites to a common domain on complement receptor type 2.
Complement receptor type 2 (CR2;CD21), a member of the superfamily of proteins containing short consensus repeats (SCRs), is the B cell receptor for both the gp350/220 envelope protein of Epstein-Barr virus (EBV), and for the C3dg protein of complement. By analysis of CR2 deletion mutants and chimeras formed with CR1 (CD35) we determined that of the 15 SCRs in CR2, the NH2-terminal two SCRs are necessary and sufficient to bind both gp350/220 and C3dg with affinities equivalent to those of the wild-type receptor. The epitope for OKB-7, a mAb that blocks binding of both EBV and C3dg and shares with these ligands B cell-activating capabilities, also requires both SCR-1 and SCR-2, whereas mAbs lacking these functions bind to other SCRs. Thus, EBV, a polyclonal activator of B cells, has selected a site that is proximate or identical to the natural ligand binding site in CR2, perhaps reflecting the relative immutability of that site as well as its signal transducing function.
Lowell
C A
CA
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Klickstein
L B
LB
Carter
R H
RH
Mitchell
J A
JA
Fearon
D T
DT
Ahearn
J M
JM
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001665:Binding Sites; D002678:Chimera; D002872:Chromosome Deletion; D000939:Epitopes / Q000032:analysis; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D007739:L Cells / Q000276:immunology; D051379:Mice; D011951:Receptors, Complement / Q000378:metabolism*; D017464:Receptors, Complement 3d; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D000939:Epitopes; D011951:Receptors, Complement; D017464:Receptors, Complement 3d