Plasmodium berghei Hsp90 contains a natural immunogenic I-Ab-restricted antigen common to rodent and human Plasmodium species

Authors:

• Enders, Matthias H.
• Bayarsaikhan, Ganchimeg
• Ghilas, Sonia
• Chua, Yu Cheng
• May, Rose
• de Menezes, Maria N.
• Ge, Zhengyu
• Tan, Peck Szee
• Cozijnsen, Anton
• Mollard, Vanessa
• Yui, Katsuyuki
• McFadden, Geoffrey I.
• Lahoud, Mireille H.
• Caminschi, Irina
• Purcell, Anthony W.
• Schittenhelm, Ralf B.
• Beattie, Lynette
• Heath, William R.
• Fernandez-Ruiz, Daniel

Details:

Current Research in Immunology, Volume 2, 2021-12-31

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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 Plasmodium epitope and is responsive to both sporozoites and blood-stage P. berghei. Here, we identify a peptide within the P. berghei heat shock protein 90 as the cognate epitope recognised by PbT-II cells. We show that C57BL/6 mice infected with P. berghei 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 in vitro activated TH1-, or particularly TH2-polarised PbT-II cells improved control of P. berghei 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.