Idiotypic cascade in the human high molecular weight melanoma-associated antigen system: fine specificity and idiotypic profile of anti-anti-idiotypic monoclonal antibodies.
The mouse anti-idiotypic (anti-id) monoclonal antibody (mAb) MK2-23 bears the internal image of the determinant defined by the syngeneic immunizing anti-human high molecular weight melanoma-associated antigen (HMW-MAA) mAb 763.74, since it induces anti-HMW-MAA antibodies in syngeneic and xenogeneic hosts. To dissect the humoral immune response induced by mAb MK2-23 at the clonal level, 1351 hybridomas were generated from a BALB/c mouse immunized with mAb MK2-23. Serological and immunochemical assays showed that the anti-anti-idiotypic (anti-anti-id) mAb GH827, GH1002 and GH1081 react only with the immunizing anti-id mAb MK2-23 and that the anti-anti-id mAb GH149, GH368, GH464, GH518, GH586, GH704, GH786 and GH1151 react with both mAb MK2-23 and HMW-MAA. The eight HMW-MAA binding anti-anti-id mAb resembled mAb 763.74 in their reactivity patterns with a panel of cell lines, although the extent of reactivity was lower. Staining of surgically removed melanoma lesions detected subtle differences in the reactivity patterns of the eight HMW-MAA binding anti-anti-id mAb. This finding in conjunction with the differential ability of the eight anti-anti-id mAb to inhibit the binding of anti-HMW-MAA mAb 763.74 to melanoma cells and to mAb MK2-23 and with the different avidity of the binding to mAb MK2-23 suggest diversity in the fine specificity of the eight HMW-MAA binding anti-anti-id mAb. Like mAb 763.74, the eight HMW-MAA binding anti-anti-id mAb express the idiotopes recognized by the anti-id mAb MK2-23 and MK2-120. In contrast, the three anti-anti-id mAb GH827, GH1002 and GH1081, which do not bind HMW-MAA binding anti-anti-id mAb to the antibodies elicited by the membrane-bound HMW-MAA corroborates the validity of the use of anti-id mAb MK2-23 as an immunogen to implement active specific immunotherapy in patients with malignant melanoma.
Yang
H
H
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
Chen
Z J
ZJ
Kageshita
T
T
Yamada
M
M
Ferrone
S
S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D066298:In Vitro Techniques; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins