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

Prato, Sandro, Maxwell, Tammy, Pinzón-Charry, Alberto, Schmidt, Christopher William, Corradin, Giampietro and Lopez, Jose Alejandro (2005) MHC class I-restricted exogenous presentation of a synthetic 102-mer malaria vaccine polypeptide. European Journal of Immunology, 35 3: 681-689. doi:10.1002/eji.200425771

Author Prato, Sandro
Maxwell, Tammy
Pinzón-Charry, Alberto
Schmidt, Christopher William
Corradin, Giampietro
Lopez, Jose Alejandro
Title MHC class I-restricted exogenous presentation of a synthetic 102-mer malaria vaccine polypeptide
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
Publication date 2005-03
Sub-type Article (original research)
DOI 10.1002/eji.200425771
Volume 35
Issue 3
Start page 681
End page 689
Total pages 9
Place of publication Weinheim, Germany
Publisher Wiley
Language eng
Subject 1107 Immunology
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.
Keyword Malaria
Synthetic peptide
CTL response
Dendritic cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
ERA 2012 Admin Only
Institute for Molecular Bioscience - Publications
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Created: Wed, 11 Feb 2009, 10:26:49 EST by Ms Lynette Adams on behalf of Institute for Molecular Bioscience