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Monoclonal Idiotypic and Anti-idiotypic Antibodies to Human Immunodeficiency Virus Type 1 Envelope Glycoprotein

¹ National Laboratory for Immunology, Laboratory Centre for Disease Control, Ottawa, Ontario, Canada K1A 0L2
and² Federal Centre for AIDS, Ottawa, Ontario, Canada

Murine monoclonal antibodies (MAbs) gp41-1 (IgG2a) and gp41-2 (IgG1), directed against the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1), were produced and characterized. These MAbs recognized both gp160 and gp41 and reacted with divergent HIV-1 isolates. Surface binding assays using viable HIV-infected cells indicated that these MAbs were directed against surface-exposed epitopes. Both MAbs caused a reduction in reverse transcriptase activity. Syngeneic monoclonal anti-idiotypic antibodies (anti-ids) against gp41-1 were also generated. Six anti-ids (agp41-11 to agp41-16) were selected by ELISA using F(ab')₂ fragments of gp41-1; no reaction was observed when fragments from an irrelevant IgG2a MAb were used. Anti-ids were recognized by both gp41-1 and gp41-2 biotinylated MAbs. Competitive ELISA studies suggested that anti-ids were directed against at least three distinct idiotopes on gp41-1. All anti-ids reacted with idiotopes associated with both heavy and light chains and not with separated chains. The binding of MAbs gp41-1 and gp41-2 to HIV-infected cells was inhibited by each anti-id, except for the binding of gp41-2 which was not affected by the presence of agp41-12. Immunization of rabbits with agp41-11 and agp41-13 resulted in an antibody response against recombinant gp160. These studies indicated that these two anti-ids contain a surrogate image of the antigen recognized by gp41-1.

Received 11 June 1990; accepted 20 September 1990.