title: Identification of autoreactive CD8+ T cell responses targeting chromogranin A in humanized NOD mice and type 1 diabetes patients.
abstract: ChgA has recently been identified as the autoantigen for diabetogenic CD4(+) T cells in NOD mice and T1D patients. However, autoreactive CD8(+) T-cell responses targeting ChgA haven't been studied yet. Here several HLA-A*0201-restricted peptides derived from mChgA and hChgA were selected by an integrated computational prediction approach, followed by an HLA-A*0201 binding assay. MChgA10-19 and mChgA(43-52) peptides, which bound well with HLA-A*0201 molecule, induced significant proliferation and IFN-γ-releasing of splenocytes from diabetic NOD.β2m(null).HHD mice. Notably, flow cytometry analysis found that mChgA(10-19) and mChgA(43-52) stimulated the production of IFN-γ, perforin, and IL-17 by splenic CD8(+) T cells of diabetic NOD.β2m(null).HHD mice. Furthermore, hChgA(10-19) and hChgA(43-52)-induced IFN-γ releasing by specific CD8(+) T cells were frequently detected in recent-onset HLA-A*0201-positive T1D patients. Thus, this study demonstrated that autoreactive CD8(+) T cells targeting ChgA were present in NOD.β2m(null).HHD mice and T1D patients, and might contribute to pathogenesis of T1D through secreting proinflammatory cytokines and cytotoxic molecules.
authors.affiliation: Institute of Immunology PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Immunology PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yashu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Immunology PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Immunology PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Meng
authors.affiliation: Institute of Immunology PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Phsiology, North Sichuan Medical College, NanChong 637007, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Institute of Immunology PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. Electronic address: zhangmengjunyy@126.com.
authors.forename: Mengjun
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Immunology PLA, Third Military Medical University, Chongqing 400038, China. Electronic address: liwang118@tmmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D053379:Chromogranin A / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000276:immunology*; D054353:Perforin / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D055815:Young Adult
chemical_list: D001324:Autoantigens; D053379:Chromogranin A; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D020381:Interleukin-17; D010446:Peptide Fragments; D054353:Perforin; D007371:Interferon-gamma
keywords: Chronogranin A; Epitope; Humanized NOD mice; Type 1 diabetes