Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 46, Issue 4, Pages 885-896Publisher
WILEY
DOI: 10.1002/eji.201545748
Keywords
Antigen presenting cells; CD8(+) T cells; Liver; Plasmodium; Transporter associated with antigen processing (TAP)
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Funding
- NIH [AI46438]
- US Army Materiel Command
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MHC class I dependent CD8(+) T cells are essential for protection induced by radiationattenuated Plasmodium sporozoites (RAS) inmurine 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 naive 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-gamma(+) 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.
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