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 beta 1-, beta 2-, and alpha 1-adrenergic, D2-dopaminergic, and muscarinic receptors. In addition we have discovered that some allergic respiratory disease patients possess circulating autoantibodies to beta 2-adrenergic receptors. These antireceptor antibodies in conjunction with specific receptor affinity reagents have allowed us to isolate, purify, and begin to characterize alpha- and beta-adrenergic, dopaminergic, and muscarinic receptors. For example, immunoprecipitation of turkey erythrocyte beta 1 receptors with monoclonal antibodies yields a single polypeptide Mr 65--70 K. In contrast, purification of beta 2-adrenergic receptors using either autoantibodies or monoclonal antibodies yields a receptor species with a subunit of Mr 55--59 K. Autoantibodies to beta 2 receptors demonstrate a 50--100% homology among beta 2 receptors from humans to rats, whereas monoclonal antibody FV-104 recognizes a determinant in the ligand binding site of all beta 1 and beta 2 receptors tested to date. These data suggest that beta 1- and beta 2-adrenergic receptors may have evolved from a common ancestor, perhaps by gene duplication.