Neutralizing and Targeting Properties of a New Set of α4β7-Specific Antibodies Are Influenced by Their Isotype
| Autor: | James Arthos, Diane Razanajaoana-Doll, Stephanie Laurant, Bernard Verrier, Claudia Cicala, Katija Jelicic, Alexandre Girard, Don Van Ryk, Nicolas Rochereau, Jean-Jacques Pin, Blandine Noailly, Christian Genin, Stéphane Paul |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Integrins Anti-HIV Agents medicine.drug_class T-Lymphocytes Anti-Inflammatory Agents Inflammation Biology Virus Replication Monoclonal antibody Inflammatory bowel disease 03 medical and health sciences medicine Animals Humans Immunologic Factors Pharmacology (medical) Avidity B-Lymphocytes Mice Inbred BALB C Antibodies Monoclonal HIV Transfection medicine.disease Antibodies Neutralizing Isotype Virology In vitro Immunoglobulin Isotypes 030104 developmental biology Infectious Diseases Immunology biology.protein Antibody medicine.symptom |
| Zdroj: | JAIDS Journal of Acquired Immune Deficiency Syndromes. 75:118-127 |
| ISSN: | 1525-4135 |
| Popis: | The homing of lymphocytes to the mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or inflammatory bowel diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7 lymphocyte-specific monoclonal antibodies that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. First, 5 monoclonal antibodies (1 IgA, 1 IgM, and 4 IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells. Their ability to block gp120/α4β7 or MAdCAM-1/α4β7 interactions was then measured in vitro with human T and B lymphocytes. In vitro, the anti-α4β7 IgA isotype was found to have the highest affinity for the α4β7 heterodimer, and it significantly reduced HIV replication in retinoic acid-treated α4β7 CD4 human T cells. This α4β7-specific IgA also displayed a high avidity for human and mouse α4β7 lymphocytes in both mouse and human inflammatory colitis tissues. These new antibodies, and in particular those with mucosa-targeting isotypes such as IgA, could therefore be potential novel therapeutic tools for treating HIV and inflammatory bowel disease. |
| Databáze: | OpenAIRE |
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