title: Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1.
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.
authors: Division of Infection and Immunity, University College London, London, United Kingdom.
authors: Calogero
authors: C
authors: Tulone
authors: Anne-Marit
authors: AM
authors: Sponaas
authors: Eun-Ang
authors: EA
authors: Raiber
authors: Alethea B
authors: AB
authors: Tabor
authors: Jean
authors: J
authors: Langhorne
authors: Benny M
authors: BM
authors: Chain
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002402:Cathepsin D / Q000172:deficiency / Q000378:metabolism*; D002678:Chimera / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000276:immunology*; D052940:Merozoites / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010641:Phenotype; D016788:Plasmodium chabaudi / Q000187:drug effects / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000469:parasitology
chemical_list: D000953:Antigens, Protozoan; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1; D011480:Protease Inhibitors; D002402:Cathepsin D