Administration of noninternal image monoclonal anti-idiotypic antibodies induces idiotype-restricted responses specific for human immunodeficiency virus envelope glycoprotein epitopes.

A mouse monoclonal anti-idiotypic antibody (anti-Id), designated MC1, was generated against chimpanzee antibodies specific for a synthetic peptide corresponding to a native epitope associated with gp41 of human immunodeficiency virus (HIV). This anti-Id recognized a shared idiotope/idiotype (Id) on a second chimpanzee anti-gp41 peptide preparation but failed to detect this Id on rabbit and mouse anti-gp41 peptide antibodies induced by immunization with the gp41 synthetic peptide. The chimpanzee Id-MC1 reaction was not inhibited by either synthetic peptide or recombinant gp160 suggesting that MC1 exhibits noninternal image, Ab-2 alpha-like characteristics. Immunization of syngeneic Balb/c mice with MC1 induced an antigen-positive (Ag+) response capable of binding the synthetic peptide, recombinant gp160, and gp41, whereas MC1-immunized rabbits did not produce any detectable anti-peptide and/or anti-HIV envelope glycoprotein antibody response. The MC1-induced anti-Id response (Ab-3) in both mice and rabbits expressed a similar Id with the Ab-1, which is not normally expressed in the anti-gp41 peptide antibody response induced by the nominal antigen in Balb/c mice and in rabbits. Together, these studies indicate that a mouse monoclonal anti-Id of the Ab-2 alpha class can induce an anti-HIV response specific for a gp41 epitope defined by a synthetic peptide, which does not cross species barriers.