Lectin-like oxidized low-density lipoprotein receptor-1 delivers heat shock protein 60-fused antigen into the MHC class I presentation pathway.
Heat shock protein (Hsp) 60 elicits a potent proinflammatory response in the innate immune system and has been proposed as a danger signal of stressed or damaged cells to the immune system. Previous studies reported CD14, TLR2, and TLR4 as mediators of signaling but probably not of binding. Although the receptor for Hsp60 was proposed to be saturable and specific on macrophages, it is not well defined. In the current study, we found that lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), as a receptor for Hsp60, could bind and internalize Hsp60 via the C terminus of Hsp60. Yeast two-hybrid assay revealed that the second beta-sheet containing the long-loop region of LOX-1 played an important role in this interaction. Furthermore, LOX-1 might be engaged as a common receptor for different Hsp60 species. Bone marrow-derived dendritic cells could cross-present Hsp60-fused OVA Ag on MHC class I molecules via LOX-1. Inhibition of the recognition of Hsp60 by LOX-1 decreases Hsp60-mediated cross-presentation of OVA and specific CTL response and protective tumor immunity in vivo. Taken together, these results demonstrate that LOX-1 functions as a receptor for Hsp60 and is involved in the delivery of Hsp60-fused Ag into the MHC class I presentation pathway.
Xie
Jianhui
J
Gene Research Center, Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, China.
Zhu
Haiyan
H
Guo
Liang
L
Ruan
Yuanyuan
Y
Wang
Lan
L
Sun
Lingling
L
Zhou
Lei
L
Wu
Weibin
W
Yun
Xiaojing
X
Shen
Aiguo
A
Gu
Jianxin
J
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D045142:Cross-Priming / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000099181:Dectin-1
D000941:Antigens; D018834:Chaperonin 60; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010047:Ovalbumin; D011993:Recombinant Fusion Proteins; D051127:Scavenger Receptors, Class E; D000099181:Dectin-1; C495138:Olr1 protein, mouse