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Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1.

Tulone, C; Sponaas, AM; Raiber, EA; Tabor, AB; Langhorne, J; Chain, BM; (2011) Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1. PLOS One , 6 (10) , Article e24886. 10.1371/journal.pone.0024886. Green open access

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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.

Type: Article
Title: Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0024886
Publisher version: http://dx.doi.org/10.1371/journal.pone.0024886
Language: English
Additional information: © 2011 Tulone et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The study was supported by the Biotechnology and Biological Sciences Research Council (BB/D005469/1) under the Selective Chemical Intervention in Biological Systems initiative and by the Medical Research Council, United Kingdom, ref. U117584248. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Animals, Antibody Formation, Antigen Presentation, Antigens, Protozoan, Bone Marrow Cells, Cathepsin D, Chimera, Dendritic Cells, Erythrocytes, Histocompatibility Antigens Class II, Immunoglobulin G, Malaria, Merozoite Surface Protein 1, Merozoites, Mice, Parasitemia, Phenotype, Plasmodium chabaudi, Protease Inhibitors, Spleen
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/1329816
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