Preparation and characterization of anti-anti-idiotypic monoclonal antibody ("Ab1-like Ab3") in relation to carcinoembryonic antigen.
In order to analyze the epitope structure of carcinoembryonic antigen (CEA) and the idiotype network system, seven anti-idiotypic monoclonal antibodies (anti-Id MoAbs) were generated from a BALB/c mouse immunized with anti-CEA MoAb P1-356, which recognized a synthetic peptide P1 of CEA, domain I. These MoAbs were divided into four groups. The anti-Id MoAbs specifically reacted with MoAb P1-356, but not with any MoAb, and inhibited the binding of MoAb P1-356 to CEA, indicating that all of these anti-Id MoAbs recognized private idiotopes at the combining sites of MoAb P1-356. Polyclonal anti-anti-idiotypic antiserum (Ab3) generated with anti-Id MoAbs M315 (Ab2), blocked the binding of MoAb P1-356 (Ab1) to CEA and reacted with CEA(Ag) and synthetic peptide P1. The analysis of serological assays suggested that it contains "Ab1-like Ab3." Therefore, we prepared anti-anti-Id MoAbs using anti-Id MoAb M315. Among 13 candidates, anti-anti-Id MoAb 11B2 was selected, because it competed with MoAb P1-356 (Ab1) binding to CEA. A direct binding assay using MoAb11B2 showed that it reacted with purified CEA and with CEA synthetic peptide P1. In addition, MoAb 11B2 (Ab3) reacted with both CEA-producing cultured cells and colonic cancerous tissues in immunostaining. These results indicate that anti-anti-Id MoAb 11B2 is "Ab1-like Ab3." Therefore, it is suggested that anti-Id MoAb M315 bears an "internal image" of the MoAb P1-356-defined epitope on CEA.
Tsujisaki
Masayuki
M
Department of Internal Medicine (Section 1), Sapporo Medical University, School of Medicine, Sapporo, Japan.
Masuya
Jiro
J
Okada
Yoshimasa
Y
Jinnohara
Tsuneharu
T
Sasaki
Shigeru
S
Yachi
Akira
A
Imai
Kohzoh
K
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D001667:Binding, Competitive; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D000939:Epitopes; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007135:Immunoglobulin Variable Region; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010452:Peptide Biosynthesis / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002272:Carcinoembryonic Antigen; D000939:Epitopes; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region