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

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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 β1‐, β2‐, and β1‐adrenergic, D2‐dopaminergic, and muscarinic receptors. In addition we have discovered that some allergic respiratory disease patients possess circulating autoantibodies to β2‐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 β1 receptors with monoclonal antibodies yields a single polypeptide Mr 65–70 K. In contrast, purification of β2‐adrenergic receptors using either autoantibodies or monoclonal antibodies yields a receptor species with a subunit of Mr 55–59 K. Autoantibodies to β2 receptors demonstrate a 50–100% homology among β2 receptors from humans to rats, whereas monoclonal antibody FV‐104 recognizes a determinant in the ligand binding site of all β1 and β2 receptors tested to date. These data suggest that β1‐ and β2‐adrenergic receptors may have evolved from a common ancestor, perhaps by gene duplication.