TAP‐mediated processing of exoerythrocytic antigens is essential for protection induced with radiation‐attenuated Plasmodium sporozoites. Issue 4 (21st January 2016)

• Record Type: Journal Article
• Authors: Pichugin, Alexander; Steers, Nick; De La Vega, Patricia; Zarling, Stasya; Chalom, Isaac; Krzych, Urszula
• Is Part Of: European journal of immunology. Volume 46:Issue 4(2016)
• Page Start: 885
• Page End: 896
• Publication Date: 2016-01-21
• Subjects: Antigen presenting cells · CD8+ T cells · Liver · Plasmodium · Transporter associated with antigen processing (TAP); Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201545748
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : Immunization of TAP‐deficient mice with P. berghei radiation‐attenuated sporozoites (Pb RAS) induces expansion, activation, proliferation and IFN‐γ production by CD8 + T cells. Despite these responses, TAP‐deficient mice are not protected against experimental malaria infection. TAP‐mediated cytosolic pathway of Ag processing is necessary for sterile protection induced with Pb RAS. Abstract : MHC class I dependent CD8 + T cells are essential for protection induced by radiation‐attenuated Plasmodium sporozoites (RAS) in murine malaria models. Apart from the mechanism of activation of CD8 + T cells specific for the circumsporozoite protein, the major sporozoite antigen (Ag), CD8 + T cells specific for other exoerythrocytic Ags that have been shown to mediate protection have not been thoroughly investigated. Specifically, mechanisms of processing and presentation of exoerythrocytic Ags, which includes liver stage (LS) Ags, remain poorly understood. We hypothesize that as exogenous proteins, LS Ags are processed by mechanisms involving either the TAP‐dependent phagosomal‐to‐cytosol or TAP‐independent vacuolar pathway of cross‐presentation. We used TAP‐deficient mice to investigate whether LS Ag mediated induction of naïve CD8 + T cells and their recall during sporozoite challenge occur by the TAP‐dependent or TAP‐independent pathways. On the basis of functional attributes, CD8 + T cells were activated via the TAP‐independent pathway during immunizations with Plasmodium berghei RAS; however, IFN‐γ + CD8 + T cells previously induced by P. berghei RAS in TAP‐deficient mice failed to be recalled against sporozoite challenge and the mice became parasitemic. On the basis of these observations, we propose that TAP‐associated Ag processing is indispensable for sterile protection induced with P. berghei RAS.