The heat shock protein Gp96 links innate and specific immunity.

Among other heat shock proteins (HSPs), the ER-resident chaperone Gp96 has been described as a potent tumour vaccine in animal models. A growing list of data underlines that Gp96 triggers both arms of pathogen defence-innate and specific immunity-in a synergistic and most efficient way: It enables specific immune responses by transferring immunogenic peptides that have been acquired in the ER to the MHC class I pathway of antigen presenting cells (APCs). For this, two important features of Gp96 are required. First, its ability to bind immunogenic peptides. Secondly, its acquisition by specialized antigen presenting cells capable of inducing cellular immune responses. Due to specific receptors on the surface of APCs, this uptake from the extracellular space occurs very efficiently and rapidly. Serving the innate branch of immunity, Gp96 unspecifically activates APCs, which then provide a pro-inflammatory cytokine milieu and co-stimulation to cytotoxic T cells. Thus, Gp96 uses all resources of the immune system to trigger cytotoxic T cell responses against associated peptides.