A Subdominant CD8+Cytotoxic T Lymphocyte (CTL) Epitope from thePlasmodium yoeliiCircumsporozoite Protein Induces CTLs That Eliminate Infected Hepatocytes from Culture
| Autor: | Eileen D. Franke, Giampietro Corradin, Alessandro Sette, John B. Sacci, Stephen L. Hoffman, Scott Southwood |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Subdominant
Molecular Sequence Data Immunology Protozoan Proteins Antigens Protozoan Biology Nitric Oxide Major histocompatibility complex Microbiology Epitope Epitopes Mice Antigen Malaria Vaccines Animals Cytotoxic T cell Amino Acid Sequence Cells Cultured Mice Inbred BALB C Vaccines Synthetic Vaccination H-2 Antigens Plasmodium yoelii biology.organism_classification Virology Molecular biology Malaria Circumsporozoite protein CTL Infectious Diseases Liver biology.protein Female Parasitology Fungal and Parasitic Infections T-Lymphocytes Cytotoxic |
| Zdroj: | Infection and Immunity. 68:3403-3411 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.68.6.3403-3411.2000 |
| Popis: | Previous studies indicated that thePlasmodium yoeliicircumsporozoite protein (PyCSP) 57–70 region elicits T cells capable of eliminating infected hepatocytes in vitro. Herein, we report that the PyCSP58–67 sequence contains an H-2dbinding motif, which binds purified Kdmolecules in vitro with low affinity (3,267 nM) and encodes an H-2d-restricted cytotoxic T lymphocyte (CTL) epitope. Immunization of BALB/c mice with three doses of a multiple antigen peptide (MAP) construct containing four branches of amino acids 57 to 70 linked to a lysine-glycine core [MAP4(PyCSP57–70)] and Lipofectin as the adjuvant induced both T-cell proliferation and a peptide-specific CTL response that was PyCSP59–67 specific, H-2drestricted, and CD8+T cell dependent. Immunization with either DNA encoding the PyCSP or irradiated sporozoites demonstrated that this CTL epitope is subdominant since it is not recognized in the context of whole CSP immunization. The biological relevance of this CTL response was underlined by the demonstration that it could mediate genetically restricted, CD8+- and nitric-oxide-dependent elimination of infected hepatocytes in vitro, as well as partial protection of BALB/c mice against sporozoite challenge. These findings indicate that subdominant epitopes with low major histocompatibility complex affinity can be used to engineer epitope-based vaccines and have implications for the selection of epitopes for subunit-based vaccines. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|