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,¶
* Department of Urology,
Department of Pathology,
Department of Neurobiology, and
Department of Medicine, David Geffen School of Medicine and
¶ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095;
|| Department of Ophthalmology, Louisiana State University Health Science Center, Shreveport, LA 71130; and
# ProtTech, Inc., Norristown, PA 19403
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by a seed grant from the University of California Cancer Research Coordinating Committee, a career development award from the University of California Los Angeles Specialized Program of Research Excellence in Lung Cancer, and a grant from the Cancer Research Institute (to G.Z.).
2 Address correspondence and reprint requests to Dr. Gang Zeng, Department of Urology and Jonsson Comprehensive Cancer Center, 66-124 Center for Health Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095. E-mail: gzeng{at}mednet.ucla.edu
3 Abbreviations used in this paper: TAA, tumor-associated Ag; CRT, calreticulin; CD40L-B, CD40L-activated B cell; DC, dendritic cell; ER, endoplasmic reticulum; GAMF, FITC-labeled goat anti-mouse secondary Ab; KLH, keyhole limpet hemocyanin.
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