title: Serological and molecular characterization of mouse anti-idiotypic monoclonal antibodies elicited with the syngeneic anti-HLA-A2,28 monoclonal antibody CR11-351.
abstract: The molecular basis of the differential specificity of seven mouse anti-id mAb elicited with the syngeneic anti-HLA-A2,28 mAb CR11-351 was analyzed by comparing their specificity with their heavy and light chain variable region sequences. Of the six mAb recognizing idiotopes within the antigen combining site of mAb CR11-351, mAb T10-352, T10-440 and T10-505 recognize the same (or spatially close) idiotope(s) since they cross-inhibit each other in their binding to mAb CR11-351 and elicit syngeneic anti-anti-id antibodies with similar specificity. On the other hand, mAb T10-421, T10-649 and T10-938 appear to recognize spatially close but distinct idiotopes since they cross-inhibit each other, but elicit anti-anti-id antibodies which inhibit only the binding of the respective immunizing anti-id mAb to mAb CR11-351. mAb T8-203 is the only anti-id mAb which recognizes an idiotope outside the antigen combining site of mAb CR11-351 since it does not inhibit the binding of the latter to target cells and binds to mAb CR11-351 coated B lymphoid cells. In addition, mAb T8-203 defines an idiotope which is shared by seven anti-HLA mAb, while the remaining six anti-id mAb recognize idiotopes which are not detectable on the panel of anti-HLA mAb. mAb T10-352, T10-440 and T10-505 are highly homologous in their VH and VL regions and in their V(D)J junctions suggesting that they may be clonally related. On the other hand, mAb T8-203, T10-649 and T10-938 share some degree of homology in their VH region as all of them use J558 VH genes but differ considerably in their VL regions. Finally, mAb T10-421 is the most unrelated mAb as it utilizes VH, D, JH, VK and JK gene segments different from those of all the other anti-id mAb. These findings indicate that in the HLA-A antigenic system defined by mAb CR11-351 the main mechanism underlying the differential target specificity of syngeneic anti-id mAb is the combinatorial diversity together with the differential pairing of heavy and light chains.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
authors.forename: E A
authors.initials: EA
authors.lastname: Armandola
authors.forename: S M
authors.initials: SM
authors.lastname: Mariani
authors.forename: S
authors.initials: S
authors.lastname: Ferrone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D015234:HLA-A Antigens / Q000276:immunology*; D007114:Immunization; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015234:HLA-A Antigens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region