HIV-1 tat protein modulates the generation of cytotoxic T cell epitopes by modifying proteasome composition and enzymatic activity
| Autor: | Antonella Caputo, Mauro Marastoni, Arianna Bottoni, Angela Bonaccorsi, Eleonora Gallerani, Alessandro Canella, Barbara Ensoli, Riccardo Gavioli, Fabiola Micheletti, Paola Rimessi, Cinzia Fortini, Aurelio Cafaro, M. Fabris |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Proteasome Endopeptidase Complex
HIV Tat immunomodulation proteasome T cell Protein subunit Immunology Genetic Vectors Heterologous Epitopes T-Lymphocyte Biology immunomodulation Lymphocyte Activation Jurkat cells Epitope NO Jurkat Cells Multienzyme Complexes Catalytic Domain medicine Immunology and Allergy Cytotoxic T cell Humans Cell Line Transformed Antigen Presentation Immunodominant Epitopes InformationSystems_INFORMATIONSYSTEMSAPPLICATIONS Hydrolysis HIV Cytotoxicity Tests Immunologic Molecular biology Peptide Fragments Enzyme Activation Cysteine Endopeptidases Protein Subunits proteasome medicine.anatomical_structure Proteasome Epstein-Barr Virus Nuclear Antigens Cell culture Gene Products tat HIV-1 tat Gene Products Human Immunodeficiency Virus Tat T-Lymphocytes Cytotoxic |
| Zdroj: | ResearcherID |
| ISSN: | 0022-1767 |
| Popis: | Tat, the trans activation protein of HIV, is produced early upon infection to promote and expand HIV replication and transmission. However, Tat appears to also have effects on target cells, which may affect Ag recognition both during infection and after vaccination. In particular, Tat targets dendritic cells and induces their maturation and Ag-presenting functions, increasing Th1 T cell responses. We show in this work that Tat modifies the catalytic subunit composition of immunoproteasomes in B and T cells either expressing Tat or treated with exogenous biological active Tat protein. In particular, Tat up-regulates latent membrane protein 7 and multicatalytic endopeptidase complex like-1 subunits and down-modulates the latent membrane protein 2 subunit. These changes correlate with the increase of all three major proteolytic activities of the proteasome and result in a more efficient generation and presentation of subdominant MHC-I-binding CTL epitopes of heterologous Ags. Thus, Tat modifies the Ag processing and modulates the generation of CTL epitopes. This may have an impact on both the control of virally infected cells during HIV-1 infection and the use of Tat for vaccination strategies. |
| Databáze: | OpenAIRE |
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