Viruses attach to cells via specialized attachment proteins that interact with specific cell surface receptors (1-5). An understanding of such virus-host cell interactions may provide new insights into the pathogenesis and prevention of infectious diseases (6).The mammalian reoviruses, segmented, double-stranded RNA viruses include three serotypes (7). The segmented nature of the reovirus genome has permitted a genetic approach for the identification of the role of individual viral components in pathogenesis, making the study of virus-host interactions more amenable to direct experimentation (8). These studies have revealed that each of the three outer capsid proteins (#lc, ~1, ~r3) plays critical, distinct roles in viral virulence. One of the outer capsid proteins, al, the reovirus hemagglutinin (HA), ~ has been shown to be the reovirus cell attachment protein (9-12). Studies utilizing monoclonal antibodies have revealed that the HA is divided into three distinct domains (13, 14), one of which governs the important biologic properties of receptor interaction, recognition by cytotoxic T lymphocytes (CTL) and recognition by neutralizing antibody (15,17). Reovirus mutants at this site, selected for resistance to neutralization, are altered in cell tropism (in the nervous system) (16) and in recognition by CTL (17). Therefore, monoclonal antibodies directed to this site, block a number of important biologic properties of reovirus.That such diverse biologic properties as CTL recognition and viral neutralization localize to one part of the HA suggests that binding is restricted by a unique conformation or, alternatively, by a set of epitopes on the HA. This implies that the receptor for virus on immune CTL, the natural receptor found on neurons, and the binding moiety of neutralizing monoclonal antibodies (idiotype) share a common configuration as well.To test this possibility, syngeneic monoclonal antibodies were raised against the idiotype portion of a prototypic neutralizing monocional antibody, 9BG5 (18,19). The antiidiotype obtained has been shown to block both viral binding

Cytotoxic T lymphocyte (Tc) cell lines specific for reovirus type 3 lysed an uninfected B cell hybridoma line, 87.92.6, that expresses and secretes an anti-idiotypic antibody that reacts with an anti-viral hemagglutinin monoclonal antibody, 9BG5. Monoclonal anti-idiotype 87.92.6 was shown by fluorescence analysis to specifically bind to reovirus Tc and to block reovirus-specific Tc from killing reovirus-infected target cells or the 87.92.6 hybridoma. An anti-LFA-1 monoclonal antibody, M17, interfered with Tc-mediated lysis of reovirus-infected targets and the 87.92.6 cells, indicating the similarity of cellular interactions mediated by LFA-1 structures when Tc bind to virally infected targets or 87.92.6 targets. Together with studies in which anti-H2 or monoclonal idiotypic antibodies were found to interfere with reovirus-specific Tc recognition of virally infected or 87.92.6 targets, these experiments indicate that some reovirus-specific Tc have conformations in their receptor that can be recognized by anti-idiotype.