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Functional epitope analysis of the human CD11a/CD18 molecule (LFA-1, lymphocyte function-associated antigen 1)
C Vermot-Desroches1, D Rigal, S Escaich
1Immunology Laboratory, Regional Blood Transfusion Centre, Lyon, France.
Insights
This study reveals specific regions on lymphocyte function-associated antigen 1 (LFA-1) are crucial for HIV-1 syncytium formation. These findings highlight LFA-1
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus 1 (HIV-1) infection leads to T cell fusion and syncytia formation.
- CD4 receptor binding is essential for HIV-1 entry, but other molecules like lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18) also mediate cell fusion.
- Understanding LFA-1's role in HIV-1-induced syncytia is key to understanding viral transmission.
Purpose of the Study:
- To identify specific regions on the human CD11a/CD18 molecule that are important for HIV-1-induced syncytium formation.
- To investigate the interaction between LFA-1 on uninfected cells and potential ligands on HIV-1 infected cells.
Main Methods:
- Utilized a panel of monoclonal antibodies (MoAbs) against distinct domains of LFA-1 (CD11a/CD18).
- Assessed the functional activity of these MoAbs in inhibiting syncytia formation between HIV-1 infected H9.III cells and uninfected SupT1 cells.
- Tested potential LFA-1 receptors, intercellular adhesion molecule 1 (ICAM-1, CD54) and HIV-1 glycoprotein 41 (gp41), on infected cells.
Main Results:
- Not all LFA-1 epitopes are equally important for HIV-1-induced syncytium formation.
- CD11a/CD18 MoAbs inhibited syncytia formation primarily by acting on uninfected SupT1 cells.
- A CD54 MoAb partially inhibited syncytia formation, indicating ICAM-1's involvement in HIV-1-mediated cell fusion.
- CD11a/CD18 MoAbs did not inhibit the binding of HIV-1 gp41 to the cell surface.
Conclusions:
- Specific regions of LFA-1 are critical for HIV-1-induced syncytium formation.
- LFA-1 on uninfected T cells interacts with ligands, such as ICAM-1, on HIV-1 infected cells to facilitate cell fusion.
- These findings suggest LFA-1 plays a role in cell-to-cell HIV-1 transmission and infection spread.
Abstract:
After binding to the CD4 receptor, the human immunodeficiency virus 1 (HIV-1) 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/CD18) have been shown to be involved in HIV-1-mediated cell fusion. This study was designed to define regions on the human CD11a/CD18 molecule important for the HIV-1-induced syncytium formation. A CD11a/CD18 MoAb panel discriminating at least five distinct and spatially distant domains on the LFA-1 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 in HIV-1-induced syncytium formation between H9.III cells chronically infected with HIV-1 and uninfected CD4+ SupT1 cells. We also demonstrated that CD11a/CD18 MoAbs inhibit syncytia formation only at the level of the uninfected SupT1 cells, suggesting that the LFA-1 molecule expressed on SupT1 cells interacts with ligand(s) expressed on the infected H9.III cells. Two potential LFA-1 receptors on the H9.III cells were tested: the ICAM-1 molecule (intercellular adhesion molecule 1, CD54) and the HIV-1 transmembrane glycoprotein 41 (gp41). A CD54 MoAb (84H10) partially inhibited syncytia formation, thus demonstrating the involvement of the ICAM-1 molecule in the HIV-1-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.
