Abstract
Merozoite Surface Protein 1 is expressed on the surface of malaria merozoites and is important for invasion of the malaria parasite into erythrocytes. MSP1-specific CD4 T cell responses and antibody can confer protective immunity in experimental models of malaria. In this study we explore the contributions of cathepsins D and E, two aspartic proteinases previously implicated in antigen processing, to generating MSP1 CD4 T-cell epitopes for presentation. The absence of cathepsin D, a late endosome/lysosomal enzyme, is associated with a reduced presentation of MSP1 both following in vitro processing of the epitope MSP1 from infected erythrocytes by bone marrow-derived dendritic cells, and following in vivo processing by splenic CD11c+ dendritic cells. By contrast, processing and presentation of the soluble recombinant protein fragment of MSP1 is unaffected by the absence of cathepsin D, but is inhibited when both cathepsin D and E are absent. The role of different proteinases in generating the CD4 T cell repertoire, therefore, depends on the context in which an antigen is introduced to the immune system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Formation / drug effects
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Antibody Formation / immunology
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Antigen Presentation / drug effects
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Antigen Presentation / immunology*
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Antigens, Protozoan / chemistry*
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Antigens, Protozoan / immunology*
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / immunology
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Cathepsin D / deficiency
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Cathepsin D / metabolism*
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Chimera / immunology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Erythrocytes / drug effects
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Erythrocytes / parasitology
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Histocompatibility Antigens Class II / immunology
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Immunoglobulin G / immunology
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Malaria / immunology*
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Malaria / parasitology
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Merozoite Surface Protein 1 / chemistry*
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Merozoite Surface Protein 1 / immunology*
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Merozoites / drug effects
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Merozoites / immunology
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Mice
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Parasitemia / immunology
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Parasitemia / parasitology
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Phenotype
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Plasmodium chabaudi / drug effects
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Plasmodium chabaudi / immunology
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Protease Inhibitors / pharmacology
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Spleen / drug effects
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Spleen / immunology
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Spleen / parasitology
Substances
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Antigens, Protozoan
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Histocompatibility Antigens Class II
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Immunoglobulin G
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Merozoite Surface Protein 1
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Protease Inhibitors
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Cathepsin D