156 Idiotypy of Reovirus Receptors

Cell surface receptors function as specific binding structures for a wide variety of ligands, including antigens, hormones, toxins, and viruses. For recognition of antigen by B lymphocytes, the basis of receptor binding to ligand relates to the arrangement of variable regions of heavy and light immunoglobulin (Ig) chains, creating novel conformational structures in and around the binding site that are termed idiotypic determinants (1, 2). Antibodies (Ab) 1 to such Ab binding sites are termed antiidiotypic. Indeed, it is thought that anti-idiotypic Ab interact with the idiotypic elements in the binding site in a manner similar to ligand binding to those same idiotypic structures. Other types of cell surface receptors such as those used to bind hormones also are highly specific. For example, the binding of insulin to its target receptor can be blocked in some cases by antireceptor Ab (3). Moreover, it has been shown that antibody to anti-insulin Ab can mimic the effect of insulin itself (4). This observation may imply a similarity in the structural conformation of the insulin binding site to insulin binding sites on specific Ig. We have begun an investigation of viral receptor interactions using reovirus as a model in an effort to determine whether viral receptors share idiotypic determinants with Ab to the virus. Two reovirus serotypes have been defined that differ in their ability to bind to lymphoid and neuronal tissues. Specifically, reovirus type 3 causes a fatal encephalitis in newborn mice with damage to neuronal cells but sparing of ependymal cells. Reovirus type 1 causes ependymal cell damage with a resultant hydrocephalus but no neuronal damage. Using recombinant viral clones, it has been shown that this in vivo tropism is determined by the viral hemagglutinin, a product of the S1 gene (5). Identical specificity has been shown for reovirus binding to neuronal cell cultures in vitro (Dichter and Weiner, manuscript submitted for