Dendritic cell surface calreticulin is a receptor for NY-ESO-1: direct interactions between tumor-associated antigen and the innate immune system.
How the immune system recognizes endogenously arising tumors and elicits adaptive immune responses against nonmutated tumor-associated Ags is poorly understood. In search of intrinsic factors contributing to the immunogenicity of the tumor-associated Ag NY-ESO-1, we found that the NY-ESO-1 protein binds to the surface of immature dendritic cells (DC), macrophages, and monocytes, but not to that of B cells or T cells. Using immunoprecipitation coupled with tandem mass spectrometry, we isolated DC surface calreticulin as the receptor for NY-ESO-1. Calreticulin Abs blocked NY-ESO-1 binding on immature DC and its cross-presentation to CD8+ T cells in vitro. Calreticulin/NY-ESO-1 interactions provide a direct link between NY-ESO-1, the innate immune system, and, potentially, the adaptive immune response against NY-ESO-1.
Zeng
Gang
G
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. gzeng@mednet.ucla.edu
Aldridge
Michael E
ME
Tian
Xiaoli
X
Seiler
Daniel
D
Zhang
Xiaolong
X
Jin
Yusheng
Y
Rao
Jianyu
J
Li
Weidong
W
Chen
Dequan
D
Langford
Marlyn P
MP
Duggan
Chris
C
Belldegrun
Arie S
AS
Dubinett
Steven M
SM
D000951:Antigens, Neoplasm / Q000378:metabolism*; D037282:Calreticulin / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D037282:Calreticulin; D008565:Membrane Proteins; D011956:Receptors, Cell Surface