The HSC73 molecular chaperone: involvement in MHC class II antigen presentation.
Heat shock proteins (HSP) are conserved proteins, many of which share the ability for indiscriminate peptide binding and ATPase-coupled peptide release. In this paper, we show that heat shock cognate protein (HSC)73, a constitutively expressed member of the HSP70 family, could be a candidate for chaperone activity within the MHC class II presentation pathway. HSC73 expression in macrophages was shown to overlap with expression of MHC class II; overexpression of HSC73 in stable transfectants of a macrophage line markedly enhanced their presentation of exogenous Ag without affecting presentation of processing independent peptide. Ag from an exogenous source was demonstrated to associate with HSC73 in macrophages, and this association was sensitive to ATP treatment and inhibited by deoxyspergualin, an immunosuppressive agent that has previously been shown to bind specifically to HSC73. Furthermore, deoxyspergualin reduced Ag presentation by macrophages in relation to the amount of HSC73 expressed in these cells. The data are consistent with a potential role for HSC73 in binding and protecting peptides from extensive degradation and/or facilitating the kinetics of peptide transfer to MHC class II molecules.
Panjwani
N
N
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom.
Akbari
O
O
Garcia
S
S
Brazil
M
M
Stockinger
B
B
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D019085:Fluorescent Antibody Technique, Direct; D015870:Gene Expression / Q000276:immunology; D006146:Guanidines / Q000494:pharmacology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007424:Intracellular Fluid / Q000737:chemistry / Q000276:immunology; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D014162:Transfection / Q000187:drug effects
D006146:Guanidines; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; C494372:Hspa8 protein, mouse; D007166:Immunosuppressive Agents; D000255:Adenosine Triphosphate; C037258:gusperimus