Related Experiment Videos
HIV-gp120 can block CD4-class II MHC-mediated adhesion
Y Rosenstein1, S J Burakoff, S H Herrmann
1Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
Insights
Soluble HIV envelope glycoprotein (gp120) avidly binds to CD4 receptors, inhibiting T-cell immune function. This gp120 binding disrupts CD4+ T-lymphocyte interactions with antigen-presenting cells, contributing to HIV-associated immune dysfunction.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human Immunodeficiency Virus (HIV) infection causes immune dysfunction.
- Soluble HIV envelope glycoprotein (gp120) avidly binds to CD4 receptors on T-lymphocytes.
- This binding may inhibit CD4+ T-cell function, a key component of immune response.
Purpose of the Study:
- To assess the impact of gp120 binding on CD4+ T-cell function.
- To investigate the mechanism by which gp120 interferes with T-cell interactions.
- To understand the role of CD4-gp120 interaction in HIV pathogenesis.
Main Methods:
- Assessed CD4+ T-cell function by measuring conjugate formation with artificial target cells (ATC).
- ATCs were lipid vesicles engineered to display MHC class II proteins, the natural ligand for CD4.
- Measured conjugate formation over time and in the presence of varying concentrations of gp120.
Main Results:
- CD4+ T-cells formed conjugates with MHC class II+ ATC in a transient, time-dependent manner (peak at ~30 min).
- Soluble gp120 specifically blocked CD4+ T-cell conjugate formation with class II+ ATC.
- This inhibition by gp120 was concentration-dependent, demonstrating a direct interference with CD4-mediated adhesion.
Conclusions:
- T-lymphocyte adhesion mediated by CD4 is a dynamic process.
- Binding of HIV gp120 to CD4 disrupts normal T-cell adhesion and interaction with antigen-presenting cells.
- gp120-mediated inhibition of CD4 function contributes to the immune dysfunction observed in HIV infection.
Abstract:
A possible component of the immune dysfunction associated with infection by HIV is the inhibition of CD4 function resulting from the avid binding of soluble HIV envelope glycoprotein (gp120) to cell surface CD4. We assessed CD4 function by measuring the ability of CD4+ T cells to form conjugates with cell size lipid vesicles, artificial target cells (ATC), bearing the natural ligand for CD4, MHC class II proteins. Conjugate formation was a transient process with the greatest number of specific cell to ATC conjugates found after approximately 30 min of incubation at 37 degrees C. Addition of gp120 specifically blocked conjugates between CD4+ cells and class II ATC in a concentration-dependent manner. These data indicate that T lymphocyte adhesion mediated by CD4 is a dynamic event and that binding of gp120 to CD4 is able to disrupt the normal progression of the interaction between CD4+ T lymphocytes and class II+ APC.