Autoantibodies and monoclonal antibodies in the purification and molecular characterization of neurotransmitter receptors

Abstract The combination of immunological advances with membrane receptor research has promoted rapid progress in the molecular characterization of neurotransmitter receptor molecules. We have to date produced monoclonal antibodies to β 1 ‐, β 2 ‐, and β 1 ‐adrenergic, D 2 ‐dopaminergic, and muscarinic receptors. In addition we have discovered that some allergic respiratory disease patients possess circulating autoantibodies to β 2 ‐adrenergic receptors. These antireceptor antibodies in conjunction with specific receptor affinity reagents have allowed us to isolate, purify, and begin to characterize α‐ and β‐adrenergic, dopaminergic, and muscarinic receptors. For example, immunoprecipitation of turkey erythrocyte β 1 receptors with monoclonal antibodies yields a single polypeptide M r 65–70 K. In contrast, purification of β 2 ‐adrenergic receptors using either autoantibodies or monoclonal antibodies yields a receptor species with a subunit of M r 55–59 K. Autoantibodies to β 2 receptors demonstrate a 50–100% homology among β 2 receptors from humans to rats, whereas monoclonal antibody FV‐104 recognizes a determinant in the ligand binding site of all β 1 and β 2 receptors tested to date. These data suggest that β 1 ‐ and β 2 ‐adrenergic receptors may have evolved from a common ancestor, perhaps by gene duplication.