Induction of cellular immunity by immunization with novel hybrid peptides complexed to heat shock protein 70

Heat shock proteins 70 (hsp70) derived from tissues and cells can elicit cy totoxic T lymphocyte (CTL) responses against peptides bound to hsp70. Howev er, peptides can markedly differ in their affinity for hsp, and this potent ially limits the repertoire of peptides available to induce CTL by the hsp immunization. Hybrid peptides consisting of a high-affinity ligand for the peptide-binding site of hsp70 joined to T cell epitopes by a glycine-serine -glycine linker were constructed. Immunization with hybrid peptides complex ed to mouse hsp70 effectively primed specific CTL responses in mice and wer e more potent than T cell peptide epitopes alone with hsp70. In vivo immuni zation with hsp70 and hybrid peptides led to rejection of tumors expressing antigen with greater efficacy than immunization with peptide epitope plus hsp70. induction of CTL responses occurred independently of CD4(+) T cells, suggesting that immunization directly primed antigen-presenting cells to e licit CD8(+) cytotoxic T cell responses without T cell help. Both peptide/h sp70 complexes and mouse hsp70 alone were able to induce cultures of mouse bone marrow-derived dendritic cells (DC) to release cytokines, including DC from endotoxin-resistant C57BL/10Sc mice. Thus, hsp70/hybrid peptide compl exes can activate DC for cytokine release, providing a potential adjuvant e ffect that could bypass T cell help.