Evolution of heat shock protein and immunity

Abstract

Heat shock proteins (hsps) are among the most abundant intracellular proteins. Their synthesis is rapidly up-regulated by various 'stressors' including temperature, glucose deprivation, infection and cancer. Certain hsps are able to: (i). associate and chaperone a large variety of cellular peptides; (ii). be efficiently internalized by antigen presenting cells (APC) through receptor-mediated endocytosis; (iii). channel antigenic peptides they chaperone in the APC's MHC class I presentation pathway; (iv). and stimulate inflammatory cytokines, chemokines and co-stimulatory molecules through the NFkappab signaling pathway. Extracellular release of hsps upon necrotic cell death and their modulated access at the surface of some cells, can be considered as a putative 'danger' signal. Based on the ancient origins and structural conservation of hsps, it has been proposed that, the role of hsps in immunity emerged early in evolution and to be widespread in extant organisms. Data from studies with the frog Xenopus support this proposition.