Functional epitope analysis of the human CD11a/CD18 molecule (LFA-1, lymphocyte function-associated antigen 1) involved in HIV-1-induced syncytium formation
Autor: | D. Rigal, J. Bernaud, S. Escaich, C. Trepo, C. Vermot-Desroches, C. Pichoud, J. P. Lamelin |
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Rok vydání: | 1991 |
Předmět: |
T cell
Immunology Biology Cross Reactions In Vitro Techniques Binding Competitive Giant Cells Epitope Immunophenotyping Cell Fusion Epitopes Antigen medicine Humans Receptor Cells Cultured Syncytium Acquired Immunodeficiency Syndrome Cell fusion Dose-Response Relationship Drug Cell adhesion molecule virus diseases Antibodies Monoclonal hemic and immune systems General Medicine Intercellular adhesion molecule Intercellular Adhesion Molecule-1 Molecular biology HIV Envelope Protein gp41 Lymphocyte Function-Associated Antigen-1 medicine.anatomical_structure HIV-1 Cell Adhesion Molecules |
Zdroj: | Scandinavian journal of immunology. 34(4) |
ISSN: | 0300-9475 |
Popis: | After binding lo the CD4 receptor, the human Immunodeficiency virus I HIV-I)may enter the T cell and induce the formation of multinucleated giant cells (syncytia). As well as the CD4 molecule, other molecules, such as the lymphocyte function-associated antigen 1(LFA-1. CD11a/CD 18) have been shown to be involved in HIV-l-mediated cell fusion. This study was designed to define regions on the human CD1la/CD18 molecule important for the HIV-l-induced syncytium formation A CD11a/CD18 MoAb panel discriminating at least five distinct and spatially distant domains of the LFA-l molecule was used. Comparison of the functional activity of different MoAbs demonstrated that all epitopes of the LFA-1 molecule were not of equal importance m HIV-1-induced syncytium formation between H9.III cells chronically infected with HIV-1 and uninlecledCD4+ Sup T1 cells. We also demonstrated that CD11a/CD18 MoAbs inhibit syncytia formation only at the level of the uninfected Sup T1 cells, suggesting that the LPA-1 molecule expressed on Sup T1 ceils interacts with ligand(s) expressed on the infected H9. III cells. Two potential LFA-1 receptors on the H9.III cells were tested: t he ICAM-1 molecule (intercellular adhesion molecule 1.CD54)and the HIV-1 transmembrance glycoprotein41 (gp4l), A CD54 MoAb (84H10) partially inhibited syncytia formation, thus demonstrating the involvement of the ICAM-1 molecule in the HIV-l-mediated cell fusion. However, the CD11a/CD18 MoAbs do not inhibit binding of the viral envelope glycoprotein gp41 to the cell surface, irrespective of the MoAb concentration used. Although we have not been successful in identifying all candidate fusion receptors for the LFA-1 molecule, these data suggest that some LFA.-1 regions are important for syncytium formation and. therefore, in the cell-to-cell transmission of virus and in the spread of infection. |
Databáze: | OpenAIRE |
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