Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response.

Journal article

The primary humoral response produces antigen-specific antibodies so to clear the initial infection, and generates a population of corresponding memory cells to prevent infection by future encounters with the same pathogen. The continuous genetic modification of a pathogen's exterior, however, is one mechanism used to evade the immune defenses of its host. Here we describe a novel means, involving anti-idiotypic antibodies, by which the host can counteract such pathogen genetic alterations by modulation of its primary humoral response. An autoimmune response against primary antibodies, Ab1's, creates anti-idiotypic antibodies (Ab2's), some of which (designated Ab2alpha) are able to bind the Ab1/antigen complex. We have discovered that binding of Ab2alpha to its corresponding Ab1 can expand Ab1's ability to bind variations of its antigen. This expanded epitope cross-reactivity is shown not only to increase the binding activity of Ab1 but also its ability to neutralize a variant infectious virus. MAb M77 is an Ab1, which is highly strain-specific for the HIV-1 envelope protein gp120(IIIB). This Ab1 can be rendered cross-reactive and neutralizing for an otherwise resistant HIV strain by its interaction with a unique anti-idiotypic Ab2alpha (GV12). Furthermore, molecular characterization of this expanded cross-reactivity was accomplished using combinatorial phage display peptide libraries.

Authors: Denisova, G; Zerwanitzer, M; Denisov, D; Spectorman, E; Mondor, I

• Publication status: Published
• Journal: Molecular immunology
• Volume: 37
• Issue: 1-2
• Pages: 53-58
• Publication date: 2000-01-01
• DOI: 10.1016/s0161-5890(00)00022-5
• EISSN: 1872-9142
• ISSN: 0161-5890
• Language: English
• Keywords: Epitopes; HIV-1; Antibodies, Anti-Idiotypic; Mice, Inbred BALB C; HIV Envelope Protein gp120; Amino Acid Sequence; Cross Reactions; Molecular Sequence Data; Animals; Antibody Formation; Mice