Hsp90 Contains a Natural Immunogenic I-A-restricted Antigen Common to Rodent and Human Species

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 -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-A)-restricted epitope and is responsive to both sporozoites and blood-stage . Here, we identify a peptide within the heat shock protein 90 as the cognate epitope recognised by PbT-II cells. We show that C57BL/6 mice infected with blood-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 activated T1-, or particularly T2-polarised PbT-II cells improved control of parasitemia 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.