Mycobacterial heat shock proteins as vaccines - a model of facilitated antigen presentation.
Heat shock proteins (hsps) are a highly conserved family of proteins, first recognized by their upregulated expression in response to host exposure to raised temperatures. Further study has revealed that they have numerous functions in the cell, primarily as chaperones mediating both the correct folding of nascent polypeptide chains and the dissolution of aggregated protein complexes. The energy requirement for this chaperone activity is provided by the ATPase activity found in most families of hsps and thus the peptide binding capacity is controlled by ATP hydrolysis. The structural consequence of this is that hsps isolated in situ are found complexed to chaperoned peptides (hspCs). Much previous work has implicated hsps in the immune response to pathogens and recent studies have shown that the interaction of hsps with antigen presenting cells, such as dendritic cells (DCs), mediates the integration of the innate and acquired immune responses. This central role for hspCs in immunity is facilitated by their dual function in both innate immunity, with the induction of cytokines and the maturation of DCs mediated by the hsp component, and acquired immunity, with the trafficking of antigens chaperoned in hspCs for antigen presentation by the mature DCs.
Walker
K Barry
KB
Biotherapeutics Group, NIBSC, Blanche Lane, South Mimms, Potters Bar EN6 3QG, UK. kbwalker@nibsc.ac.uk
Keeble
James
J
Colaco
Camilo
C
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018448:Models, Immunological; D018832:Molecular Chaperones / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology*
D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010455:Peptides; D032581:Tuberculosis Vaccines