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* Department of Biochemistry, University of Lausanne, Epalinges, Switzerland;
Institut Cochin, Departement d’Immunologie, Hôpital Cochin, Paris, France;
Institut National de la Santé et de la Recherche Médicale, Paris, France;
Centre National de la Recherche Scientifique Unité Mixte de Recherche, Paris, France; and
¶ Université Rene Descartes, Paris, France
A substantial and protective response against malaria liver stages is directed against the circumsporozoite protein (CSP) and involves induction of CD8+ T cells and production of IFN-
. CSP-derived peptides have been shown to be presented on the surface of infected hepatocytes in the context of MHC class I molecules. However, little is known about how the CSP and other sporozoite Ags are processed and presented to CD8+ T cells. We investigated how primary hepatocytes from BALB/c mice process the CSP of Plasmodium berghei after live sporozoite infection and present CSP-derived peptides to specific H-2Kd-restricted CD8+ T cells in vitro. Using both wild-type and spect–/– P. berghei sporozoites, we show that both infected and traversed primary hepatocytes process and present the CSP. The processing and presentation pathway was found to involve the proteasome, Ag transport through a postendoplasmic reticulum compartment, and aspartic proteases. Thus, it can be hypothesized that infected hepatocytes can contribute in vivo to the elicitation and expansion of a T cell response.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by European Community Grant QLK 2-CT-2002-00700.
2 Address correspondence and reprint requests to Dr. Giampietro Corradin, Department of Biochemistry, Chemin des Boveresses 155, Epalinges, Switzerland. E-mail address: Giampietro.Corradin{at}unil.ch
3 Abbreviations used in this paper: CSP, circumsporozoite; SPECT, sporozoite microneme protein essential for cell traversal; wt, wild type; BFA, brefeldin A; LLnL, N-acetyl-L-leucyl-L-leucyl-L-norleucinal; Cbz-LLL, carbobenzoxyl-leucinyl-leucinyl-leucinal; ICS, intracellular cytokine staining; RT, room temperature; DAPI, 4',6'-diamidino-2-phenylindole; EEF, exoerythrocytic form; GdCl, gadolinium chloride; DC, dendritic cell; HSP, heat shock protein.
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