Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response.
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.
Denisova
G F
GF
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Zerwanitzer
M
M
Denisov
D A
DA
Spectorman
E
E
Mondor
I
I
Sattentau
Q
Q
Gershoni
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000917:Antibody Formation; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data
D000888:Antibodies, Anti-Idiotypic; D000939:Epitopes; D015699:HIV Envelope Protein gp120