title: TAP-mediated processing of exoerythrocytic antigens is essential for protection induced with radiation-attenuated Plasmodium sporozoites.
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.
authors.affiliation: Department of Cellular Immunology, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pichugin
authors.affiliation: Department of Cellular Immunology, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Steers
authors.affiliation: Department of Cellular Immunology, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: De La Vega
authors.affiliation: Department of Cellular Immunology, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Stasya
authors.initials: S
authors.lastname: Zarling
authors.affiliation: Department of Cellular Immunology, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Chalom
authors.affiliation: Department of Cellular Immunology, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Urszula
authors.initials: U
authors.lastname: Krzych
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei / Q000276:immunology* / Q000528:radiation effects; D015800:Protozoan Proteins / Q000276:immunology; D034101:Sporozoites / Q000276:immunology* / Q000528:radiation effects
chemical_list: D018528:ATP-Binding Cassette Transporters; D000953:Antigens, Protozoan; D015395:Histocompatibility Antigens Class I; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; C477327:transporter associated with antigen processing (TAP); D007371:Interferon-gamma
keywords: Antigen presenting cells · CD8+ T cells · Liver · Plasmodium · Transporter associated with antigen processing (TAP)