title: The lectin Siglec-G inhibits dendritic cell cross-presentation by impairing MHC class I-peptide complex formation.
abstract: CD8α(+) dendritic cells (DCs) are specialized at cross-presenting extracellular antigens on major histocompatibility complex (MHC) class I molecules to initiate cytotoxic T lymphocyte (CTL) responses; however, details of the mechanisms that regulate cross-presentation remain unknown. We found lower expression of the lectin family member Siglec-G in CD8α(+) DCs, and Siglec-G deficient (Siglecg(-/-)) mice generated more antigen-specific CTLs to inhibit intracellular bacterial infection and tumor growth. MHC class I-peptide complexes were more abundant on Siglecg(-/-) CD8α(+) DCs than on Siglecg(+/+) CD8α(+) DCs. Mechanistically, phagosome-expressed Siglec-G recruited the phosphatase SHP-1, which dephosphorylated the NADPH oxidase component p47(phox) and inhibited the activation of NOX2 on phagosomes. This resulted in excessive hydrolysis of exogenous antigens, which led to diminished formation of MHC class I-peptide complexes for cross-presentation. Therefore, Siglec-G inhibited DC cross-presentation by impairing such complex formation, and our results add insight into the regulation of cross-presentation in adaptive immunity.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.|National Key Laboratory of Medical Immunology &Institute of Immunology, Second Military Medical University, Shanghai, China.|National Key Laboratory of Medical Molecular Biology &Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: National Key Laboratory of Medical Immunology &Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Molecular Biology &Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: National Key Laboratory of Medical Immunology &Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Immunology &Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Xiongfei
authors.initials: X
authors.lastname: Xu
authors.affiliation: National Key Laboratory of Medical Immunology &Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: National Key Laboratory of Medical Immunology &Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Molecular Biology &Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.|National Key Laboratory of Medical Immunology &Institute of Immunology, Second Military Medical University, Shanghai, China.|National Key Laboratory of Medical Molecular Biology &Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000276:immunology*; D010446:Peptide Fragments / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D047368:Tumor Burden / Q000235:genetics
chemical_list: D000941:Antigens; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D015395:Histocompatibility Antigens Class I; D037102:Lectins; D010446:Peptide Fragments; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6