MHC class I-restricted exogenous presentation of a synthetic 102-mer malaria vaccine polypeptide

Details

Serval ID
serval:BIB_BD214ADB2463
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
MHC class I-restricted exogenous presentation of a synthetic 102-mer malaria vaccine polypeptide
Journal
European Journal of Immunology
Author(s)
Prato  S., Maxwell  T., Pinzon-Charry  A., Schmidt  C. W., Corradin  G., Lopez  J. A.
ISSN
0014-2980 (Print)
Publication state
Published
Issued date
03/2005
Volume
35
Number
3
Pages
681-9
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Abstract
The circumsporozoite (CS) is the most abundant surface protein of the Plasmodium sporozoite, and is also present early in the liver stage of the infection. Following successful protective experiments in mice and monkeys, the synthetic 102-mer malaria vaccine polypeptide representing the C-terminal region of the CS of Plasmodium falciparum was tested in a clinical trial with healthy human volunteers. This vaccine induced strong CD8(+), CD4(+) T lymphocyte and antibody responses specific for the immunizing peptide. CD8(+) T lymphocyte responses elicited in HLA-A*0201 volunteers recognized two well-defined cytotoxic T lymphocyte epitopes within the CS. Here, we show that both monocyte-derived dendritic cells (Mo-DC) and Epstein-Barr virus-transformed B-lymphoblastoid cells (LCL) can present a cytotoxic T lymphocyte epitope contained within the 102-mer synthetic peptide. Paraformaldehyde and low temperature inhibited presentation, indicating that cellular processing was required. Using specific inhibitors, we show that, in both cell types, processing requires the proteasome and the MHC class I pathway, while the endosomal compartment appears to be critical only for the presentation by Mo-DC. Antigen uptake is associated with actin polymerization in both cell types. These in vitro results demonstrate the likely pathway of antigen presentation achieved via vaccination with this synthetic peptide.
Keywords
Animals Antigen Presentation/*immunology B-Lymphocytes/immunology/virology Dendritic Cells/immunology Epitopes, T-Lymphocyte/immunology Flow Cytometry Herpesvirus 4, Human Histocompatibility Antigens Class I/*immunology Humans Malaria Vaccines/*immunology Peptides/*immunology Plasmodium falciparum/*immunology Protozoan Proteins/immunology Vaccines, Synthetic
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:55
Last modification date
20/08/2019 15:31
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