Heat shock protein-peptide complexes for use in vaccines

Abstract

The heat shock proteins gp96, HSP70, and HSP90 are complexed to a diverse array of cellular proteins and peptides as a consequence of their chaperone functions. There is good experimental evidence that vaccination with these heat shock protein-peptide complexes elicit immune responses against chaperoned peptide antigens. As shown with gp96, this requires internalization of the heat shock protein-peptide complexes by macrophages and processing of the chaperoned peptides for class I restricted presentation. Via this process, primarily CD8+ antigen-specific T cells are primed by gp96 vaccination. This might represent a general mechanism for priming of MHC-class I restricted T cells by professional antigen-presenting cells. At least gp96 has been shown to be associated with peptides that are not selected by the MHC haplotype of the harboring cell. This allows for immunization with gp96-peptide complexes across MHC barriers, for example against shared tumor antigens or viral antigens.