Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity.
Microbial HSP70 (heat-shock protein 70) consists of three functionally distinct domains: an N-terminal 44 kDa ATPase portion (amino acids 1-358), followed by an 18 kDa peptide-binding domain (amino acids 359-494) and a C-terminal 10 kDa fragment (amino acids 495-609). Immunological functions of these three different domains in stimulating monocytes and dendritic cells have not been fully defined. However, the C-terminal portion (amino acids 359-610) stimulates the production of CC chemokines, IL-12 (interleukin-12), TNFalpha(tumour necrosis factor alpha), NO and maturation of dendritic cells and also functions as an adjuvant in the induction of immune responses. In contrast, the ATPase domain of microbial HSP70 mostly lacks these functions. Since the receptor for HSP70 is CD40, which with its CD40 ligand constitutes a major co-stimulatory pathway in the interaction between antigen-presenting cells and T-cells, HSP70 may function as an alternative ligand to CD40L. HSP70-CD40 interaction has been demonstrated in non-human primates to play a role in HIV infection, in protection against Mycobacterium tuberculosis and in conversion of tolerance to immunity.
Mucosal Immunology Unit, Guy's, King's and St. Thomas' Hospital Medical and Dental Schools, London SE1 9RT, UK. thomas.lehner@kcl.ac.uk
T
T
Lehner
Y
Y
Wang
T
T
Whittall
E
E
McGowan
C G
CG
Kelly
M
M
Singh
D000222:Adaptation, Physiological / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology; D019013:CD40 Antigens / Q000502:physiology*; D018925:Chemokines / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000502:physiology*; D006860:Hydrogen Bonding; D007113:Immunity, Innate
D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D019013:CD40 Antigens; D018925:Chemokines; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins