Plasmodium berghei-infected primary hepatocytes process and present the circumsporozoite protein to specific CD8+ T cells in vitro.
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-gamma. 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-2K(d)-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.
Bongfen
Silayuv E
SE
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Torgler
Ralph
R
Romero
Jackeline F
JF
Renia
Laurent
L
Corradin
Giampietro
G
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D016282:Aspartic Acid Endopeptidases / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D022781:Hepatocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D016282:Aspartic Acid Endopeptidases; D046988:Proteasome Endopeptidase Complex