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,...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2000
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| _version_ | 1826263881619603456 |
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| author | Denisova, G Zerwanitzer, M Denisov, D Spectorman, E Mondor, I Sattentau, Q Gershoni, J |
| author_facet | Denisova, G Zerwanitzer, M Denisov, D Spectorman, E Mondor, I Sattentau, Q Gershoni, J |
| author_sort | Denisova, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:58:55Z |
| format | Journal article |
| id | oxford-uuid:26986538-b0fe-413a-a463-d75d92ca0e93 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:58:55Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:26986538-b0fe-413a-a463-d75d92ca0e932022-03-26T12:01:58ZExpansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:26986538-b0fe-413a-a463-d75d92ca0e93EnglishSymplectic Elements at Oxford2000Denisova, GZerwanitzer, MDenisov, DSpectorman, EMondor, ISattentau, QGershoni, JThe 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. |
| spellingShingle | Denisova, G Zerwanitzer, M Denisov, D Spectorman, E Mondor, I Sattentau, Q Gershoni, J Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response. |
| title | Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response. |
| title_full | Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response. |
| title_fullStr | Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response. |
| title_full_unstemmed | Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response. |
| title_short | Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response. |
| title_sort | expansion of epitope cross reactivity by anti idiotype modulation of the primary humoral response |
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