Blood-Stage Plasmodium berghei Infection Generates a Potent, Specific CD81 T-Cell Response Despite Residence Largely in Cells Lacking MHC I Processing Machinery

Murine cerebral malaria is a complex disease caused by Plasmodium berghei ANKA infection. Several cell types, including CD81 T cells, are essential effectors of disease. Although the use of transgenic parasites expressing model antigens has revealed the induction of cytotoxic T lymphocytes (CTL) specific for these model antigens, there is no direct evidence for a response to authentic blood-stage parasite antigens, nor any knowledge of its magnitude. Our studies show that there is a dramatic primary parasite-specific CTL response, akin to viral immunity, reaching approximately 30 % of splenic CD81 T cells, with many producing interferon-c and tumor necrosis factor–a. These cells express granzyme B and other markers of specific responders, are cytolytic, and respond to a broad array of major histocompatibility complex (MHC) I–restricted epitopes, 5 of which are identified here. Our studies indicate that vigorous CTL responses can be induced to pathogens even when they largely reside in red blood cells, which lack MHC I processing machinery. Most cases of human malaria are caused by 2 main Plasmodium species, P. falciparum and P. vivax. Like humans, rodents have their own specific Plasmodium species, which cause varying forms of malarial disease. One such pathogen, Plasmodium berghei ANKA (PbA)