Plasmodium bergheiHsp90 contains a natural immunogenic I-Ab-restricted antigen common to rodent and human Plasmodiumspecies

Thorough understanding of the role of CD4 T cells in immunity can be greatly assisted by the study of responses to defined specificities. This requires knowledge of Plasmodium-derived immunogenic epitopes, of which only a few have been identified, especially for the mouse C57BL/6 background. We recently developed a TCR transgenic mouse line, termed PbT-II, that produces CD4+T cells specific for an MHC class II (I-Ab)-restricted Plasmodiumepitope and is responsive to both sporozoites and blood-stage P. berghei. Here, we identify a peptide within the P. bergheiheat shock protein 90 as the cognate epitope recognised by PbT-II cells. We show that C57BL/6 mice infected with P. bergheiblood-stage induce an endogenous CD4 T cell response specific for this epitope, indicating cells of similar specificity to PbT-II cells are present in the naïve repertoire. Adoptive transfer of in vitroactivated TH1-, or particularly TH2-polarised PbT-II cells improved control of P. bergheiparasitemia in C57BL/6 mice and drastically reduced the onset of experimental cerebral malaria. Our results identify a versatile, potentially protective MHC-II restricted epitope useful for exploration of CD4 T cell-mediated immunity and vaccination strategies against malaria.