The second face of HSPs: a review of key functions in the immune system

Heat shock proteins (HSPs) are an abundant class of proteins well known for their functions in protein folding and molecular chaperoning within all compartments of a cell. These functions are fundamental in all single and multicellular organisms, and so HSPs have remained relatively conserved in structure throughout evolution. The ability of select members of the HSP family to chaperone peptides and molecules associated with host defense against internal and external threats means that the HSPs have an important role in the immune system. We discuss the roles of HSPs that are integral to pathways of Ag transfer between cells, Ag presentation by MHC molecules, stimulation of innate immune responses, expression of innate immune receptors, cancer and viral immunology, and autoimmunity. The ample appreciation for these roles of HSPs in the immune system has led to the development and testing of HSPs both as therapeutics and targets for various diseases. These discoveries have been made with only a handful of the HSPs, suggesting a significant number of immune functions of other HSPs remain uncharted.