Anti-idiotypic antibodies to a polyomavirus monoclonal antibody recognize cell surface components of mouse kidney cells and prevent polyomavirus infection

Abstract

Anti-idiotypic antibodies have been successfully used to identify and isolate the receptor for several cell ligands. To prepare an immunologic probe for identification of the polyomavirus receptor on mouse kidney cells, polyclonal antisera against antipolyomavirus antibodies were prepared in rabbits. Fab fragments of the previously characterized monoclonal antibody E7, which neutralizes polyomavirus infection, were used for immunization (S. J. Marriott and R. A. Consigli, J. Virol. 56:365-372, 1985). Sera containing the greatest anti-idiotype activity were identified by enzyme-linked immunosorbent assay (ELISA) and purified by a series of affinity columns. The anti-idiotypic antibodies recognized the E7 idiotope in an ELISA, and anti-idiotype binding could be inhibited by preincubation of E7 monoclonal antibody with polyomavirus virions. When mixed with anti-idiotype immunoglobulin G (IgG), E7 was no longer capable of binding or immunoprecipitating polyomavirus virions or neutralizing polyomavirus infection. Direct immunofluorescence showed antiidiotype IgG reactivity with a cell surface component of mouse kidney cells. Anti-idiotype F(ab')2 effectively competed with polyomavirus for binding to mouse kidney cells and displayed binding kinetics similar to those of polyomavirus. Virus infection of mouse kidney cells was blocked in a dose-dependent manner following treatment of the cells with anti-idiotype IgG. The anti-idiotype identified several proteins (95, 50, and 24 to 31 kilodaltons) in an immunoblot of mouse kidney cell membrane proteins but reacted predominantly with a single 50-kilodalton protein in a radioimmunoassay. The anti-idiotype failed to react with virus proteins in three assays, including ELISA, immunoprecipitation, and immunoblotting. The implications of this work for future identification and characterization of the polyomavirus receptor on mouse kidney cells are discussed.

Fibronectin of human liver sinusoids binds hepatitis B virus: identification by an anti-idiotypic antibody bearing the internal image of the pre-S2 domain

“…Several investigators have recently used the vast molecular repertoire of antibody molecules as mimics of ligands for a variety of hormonal and neurotransmitter receptors (12,23,41,42). Induction of anti-Ids has also been considered as an alternative approach for identification of viral receptors (5,12,19,23,24,41,42,45). However, this question remains open, since in other studies, anti-Ids failed to identify viral receptors (1), and in the reciprocal system, anti-Ids produced against anti-receptor antibodies did not recognize viral attachment proteins (6).…”

Identification of a putative alphavirus receptor on mouse neural cells

“…An anti-idiotypic antibody made against a MAb which interacts with a virus at the site of virus binding to the host cell surface may provide an internal image of the cell attachment site and provide a reagent to identify the cellular receptor. Anti-idiotypic antibodies have proven useful in the identification of cellular receptors for polyomavirus, reovirus type 3, and leukemogenic retrovirus (3,16,27,32). We have identified a candidate receptor for SV by using an anti-idiotypic antibody raised against neutralizing MAb 209, which maps by competitive binding to epitope E2-c.…”

The Polyomaviridae: Contributions of virus structure to our understanding of virus receptors and infectious entry

“…Antibodies raised against virions that were found to be neutralizing specifically recognized species D, E, and F supporting this hypothesis (Bolen et al, 1981). The group then went on to attempt isolation of cellular receptors for mPyV by preparing anti-idiotypic antibodies to VP1 (Marriott and Consigli, 1985;Marriott et al, 1987). These antibodies blocked infection and pulled down several proteins associated with cell surfaces.…”