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

摘要

Heat shock proteins 70 (hsp70) derived from tissues and cells can elicit cytotoxic T lymphocyte (CTL) responses against peptides beund to hsp70. However, peptides can markedly differ in their affinity for hsp, and this potentially limits the repertoire of pep- tides 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 pep- hdes complexed to mouse hsp70 effectively primed specific CTL responses in mice and were more potent than T cell peptide epitopes alone with hsi70. In vivo immunization with hsp70 and hybrid peptides led to.rejection of tumors expressing antigen with gleater 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 elicit CD8+ cytotoxic T cell responses without T cell help. Both peptide/hsp70 complexes and mouse hsp70 alone were able to induce Cultures of mouse bone marrow-derived dsndritic cells (DC) to release cytokines, including DC from endo- toxin-resistant C57BL/10Sc mice. Thus. hsp70/hybrid peptide com- lexes can activate DC for cytokine release. providing a potential adjuvant effect that could bypass T cell help.