The immune response toward beta-adrenergic ligands and their receptors. VIII. Extensive diversity of VH and VL genes encoding anti-alprenolol antibodies.
The V region genes (VH and VL) used in the immune response of BALB/c mice to alprenolol, a synthetic beta-adrenergic ligand, were examined by Southern blot and nucleotide sequence analyses. Fourteen anti-alprenolol hybridomas utilize 10 different combinations of six Vk, one V lambda, eight VH, three JK, one J lambda, and three JH genes. In addition to the combinatorial association, somatic mutations and junctional variation of assembled genes further contribute to diversity of the anti-alprenolol response. Although differing both in length and structure, the five H-chain third complementarity-determining region analyzed contain several acidic residues. Neither V gene utilization, nor H-chain third complementarity-determining-region structure can be simply correlated with affinity of the antibodies for the ligand. The anti-alprenolol V genes were compared with the corresponding sequences of unrelated antibodies. Antibody 37A4 shares a VH gene with anti-(Glu60Ala30Tyr10)n random terpolymer and anti-nitrophenyl antibodies, and a Vk gene with two anti-oxazolone antibodies. Antibodies 14C3 and 17C1 use the same germ-line VH and Vk genes as do anti-anti-idiotypic antibodies of the (Glu60Ala30Tyr10) system. These data demonstrate the genetic diversity of the antibody response to alprenolol, and illustrate the extensive flexibility of the immune system.
D000526:Alprenolol / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D000916:Antibody Diversity; D001483:Base Sequence; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D000526:Alprenolol