Serologic and molecular characterization of the T15 idiotype--II. Structural basis of independent idiotope expression on phosphorylcholine-specific monoclonal antibodies.
We examined the expression of T15 idiotopes (Id) on phosphorylcholine (PC)-binding monoclonal immunoglobulins and defined the structural correlates of these Id. The seven monoclonal anti-Id antibodies used as probes recognize distinct determinants that range from the antigen binding site to the CH1 domain on TEPC15. Competition between a series of PC-specific immunoglobulins and radiolabelled TEPC15 for binding to anti-Id in solid phase revealed a broad spectrum of idiotopic crossreactivity. A strong crossreactivity with TEPC15 was observed only in proteins possessing the VK22 light chain. Each of the seven discrete, overlapping T15 Id may be expressed independently of each other on PC-binding immunoglobulins, indicating a significant idiotopic heterogeneity among T15 B-cell clones. No correlation was found between the public (shared) expression of an Id and its position relative to the antigen-binding site. Variations in the primary sequences of PC-binding immunoglobulins were correlated with their effect on individual Id expression. Regions influencing the expression of three Id were localized on a computer display of the three-dimensional structure of the closely related PC-binding myeloma protein McPC603. These data show that some, but not all individual Id determinants may be influenced by amino acid substitutions in the first and third hypervariable loops.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis*; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D002794:Choline / Q000031:analogs & derivatives*; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009194:Myeloma Proteins / Q000276:immunology*; D010767:Phosphorylcholine / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D009194:Myeloma Proteins; D010767:Phosphorylcholine; D002794:Choline