Abstract

Induction of long-lasting protective immunity to malaria by repetitive immunization with P. berghei γ radiation-attenuated sporozoites (γ-spz) requires MHC class I-restricted CD8+ T cells, implying that γ-spz/liver stage derived antigens have to be presented through one of the cross-presentation pathways. Based on accumulation of proliferating and IFN-γ producing effector/memory CD8+ T cells in the livers of TAP−/− mice, we showed that TAP-independent vacuolar pathway efficiently operates in vivo during priming and subsequent boosts with γ-spz. Likewise, infectious sporozoite challenge increased the number of IFN-γ+ CD8+ T cells in γ-spz immune TAP−/− mice and induced IFN-γ production by wt γ-spz immune CD8+ T cells transferred into TAP−/− environment suggesting that γ-spz/liver stage derived MHC class I specific peptides generated in a TAP-independent manner participate in response to infectious sporozoites. Nevertheless, the pattern of IFN-γ secretion, parasitemia and survival data upon infectious sporozoite challenge clearly indicated that TAP-associated antigen processing is indispensable for sterile protection.

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