A role for the Hsp90 molecular chaperone family in antigen presentation to T lymphocytes via major histocompatibility complex class II molecules
| Autor: | Anna George, Satyajit Rath, Satyajit Mayor, Vineeta Bal, Deepa Rajagopal |
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| Rok vydání: | 2006 |
| Předmět: |
Lactams
Macrocyclic T-Lymphocytes Blotting Western Immunology Antigen presentation chemical and pharmacologic phenomena Biology Lymphocyte Activation Major histocompatibility complex Cell Line Interferon-gamma Mice Antigen Transduction Genetic Heat shock protein MHC class I Benzoquinones polycyclic compounds Animals Humans Immunology and Allergy HSP90 Heat-Shock Proteins Enzyme Inhibitors Antigen-presenting cell Antigen Presentation Antigen processing Macrophages T-cell receptor Histocompatibility Antigens Class II Quinones respiratory system Flow Cytometry Molecular biology Cell biology biology.protein Electrophoresis Polyacrylamide Gel |
| Zdroj: | European Journal of Immunology. 36:828-841 |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | The heat shock protein (HSP) Hsp90 is known to chaperone cytosolic peptides for MHC class I (MHCI)-restricted antigen presentation to T lymphocytes. We now demonstrate a role for Hsp90 activity in presentation of antigens on MHCII. Treatment of mouse antigen-presenting cells (APC) with the pharmacological Hsp90 inhibitor, geldanamycin, inhibited MHCII-mediated presentation of endocytosed and cytosolic proteins as well as synthetic peptides to specific T cells. Ectopic expression of human Hsp90 in APC enhanced MHCII-mediated antigen presentation. Further, pharmacological Hsp90 inhibition reduced, while retroviral Hsp90 overexpression enhanced, the levels of stable compact MHCII heterodimers correlating with the antigen presentation phenotype. Pharmacological inhibition of Hsp90 activity in IFN-gamma-treated APC resulted in severe abrogation of MHCII-restricted presentation of cytosolic antigen, but only partially inhibited exogenous antigen presentation. Our data suggest a major role for Hsp90 activity in MHCII-mediated antigen presentation pathways, and implicate IFN-gamma-inducible Hsp90-independent mechanisms. |
| Databáze: | OpenAIRE |
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