The association of various D elements with a single-immunoglobulin VH gene segment: influence on the expression of a major cross-reactive idiotype.
A large fraction of the anti-p-azophenylarsonate antibodies of strain A/J mice share a major cross-reactive idiotype (IdCR). Structural analysis of monoclonal antibodies expressing this idiotype (IdCR+) indicates that a particular combination of variable region gene segments (Vk, Jk, VH, D, and JH) encodes the variable regions of the light and heavy chains of these IdCR+ antibodies. With the use of serologic methods, hybridoma cell lines have been isolated that produce monoclonal antibodies lacking IdCR determinants (IdCR-), but that are derived from most of the same combination of variable region gene segments that encode IdCR+ monoclonal antibodies. Structural analysis of these IdCR- monoclonal antibodies demonstrates that they are very homologous to each other and to IdCR+ monoclonal antibodies with respect to VH and VL sequences, but are markedly different from IdCR+ monoclonal antibodies in their utilization of D region segments. Comparisons of antigen avidity of these IdCR+ and IdCR- antibodies indicates that conservation of D region structure is not crucial for effective antigen binding. These results indicate the importance of the D region in idiotypy in the IdCR system and demonstrate the variation permitted in D region structure while maintaining antigen recognition.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000916:Antibody Diversity; D000937:Antigen-Antibody Reactions; D001391:Azo Compounds / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D002469:Cell Separation; D003429:Cross Reactions; D006825:Hybridomas / Q000032:analysis / Q000378:metabolism; D007106:Immune Sera / Q000032:analysis; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000032:analysis; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D011817:Rabbits; D010132:p-Azobenzenearsonate / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001391:Azo Compounds; D007106:Immune Sera; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D010132:p-Azobenzenearsonate