differential requirement for cathepsin d for processing of the full length and c-terminal fragment of the malaria antigen msp1微分要求组织蛋白酶d处理的完整长度和c端片段疟疾抗原msp1.pdfVIP

Differential Requirement for Cathepsin D for Processing of the Full Length and C-Terminal Fragment of the Malaria Antigen MSP1 1. 2. 3 3 2 Calogero Tulone , Anne-Marit Sponaas , Eun-Ang Raiber , Alethea B. Tabor , Jean Langhorne , Benny M. Chain1* 1 Division of Infection and Immunity, University College London, London, United Kingdom, 2 Division of Parasitology MRC National Institute of Medical Research, London, United Kingdom, 3 Department of Chemistry, University College London, London, United Kingdom 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. Citation: Tulone C, Sponaas A-M, Raiber E-A, Tabor AB, Langhorne J, et al. (2011) Differe