Molecular mechanism of vaccination effect induced by stress protein-Malaria CS antigen

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Immunization with gp96 and hsc70 that bound naturally occurring peptides in vivo or bound synthetic peptides by in vitro reconstitution, have been shown to induce peptide specific CTLs. In addition, mycobacterial hsp70 covalently fused to OVA-derived fragments was shown to generate MHC class I restricted CL responses. In the present study, five different CTL epitopes, including peptides derived from Plasmodium yoelii circumsporozoite protein, tumor antigens, HY antigen and OVA, were genetically fused either to N or C terminus of murine heat shock cognate protein 70 (hsc70), and expressed in E.coli. Peptide specific CTLs were induced by vaccination with all the fusion proteins, indicating that no cognate flanking regions of CTL epitopes are necessary. A root of injection was crucial for CIL induction. CD4^+ T cells were not required for the priming of CD8^+ T cells, and vaccination with bone-marrow derived dendritic cells pulsed with fusion proteins also elicited CL responses. Furthermore, by using deletion mutants of hsc70, the most responsible region of hsc70 to generate CTLs was mapped to hsc70_<280-385>.