Immunoadjuvant chaperone, GRP170, induces 'danger signals' upon interaction with dendritic cells.
When chaperoning tumour antigens, glucose-regulated protein 170 (GRP170) is capable of inducing effective antitumour immune responses. In the present study, we determined whether such immunoadjuvant properties of GRP170 also involve the ability to induce 'danger signals' through interaction with APC. We prepared recombinant GRP170 in the baculovirus expression system with low endotoxin concentration at which LPS did not have any effect on dendritic cells (DC). We showed that GRP170 binds DC in a receptor-mediated fashion and induces DC to upregulate the expression of MHC class II, CD86 and CD40 molecules, and to secrete pro-inflammatory cytokines. GRP170 also induced expression of CD40 molecules in a B16F10 cell line, whereas LPS failed to do so. These findings show that GRP170 acts as a danger signal through its interaction with DC, regardless of its endotoxin component.
Manjili
Masoud H
MH
Department of Microbiology and Immunology, Virginia Commonwealth University, Massey Cancer Centre, Richmond, Virginia 23298, USA. mmanjili@vcu.edu
Park
Jun-Eui
JE
Facciponte
John G
JG
Wang
Xiang-Yang
XY
Subjeck
John R
JR
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D006023:Glycoproteins; D018840:HSP70 Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; C098410:glucose-regulated protein 170