Dendritic cell surface calreticulin is a receptor for NY-ESO-1: direct interactions between tumor-associated antigen and the innate immune system |
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Authors: | Zeng Gang Aldridge Michael E Tian Xiaoli Seiler Daniel Zhang Xiaolong Jin Yusheng Rao Jianyu Li Weidong Chen Dequan Langford Marlyn P Duggan Chris Belldegrun Arie S Dubinett Steven M |
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Institution: | Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. gzeng@mednet.ucla.edu |
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Abstract: | 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. |
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