Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes

Xinyu Xu; Yong Gu; Lingling Bian; Yun Shi; Yun Cai; Yang Chen; Heng Chen; Li Qian; Xiangmei Wu; Kuanfeng Xu; Roberto Mallone; Howard W. Davidson; Liping Yu; Jin-Xiong She; Mei Zhang; Tao Yang

doi:10.1016/j.vaccine.2015.10.108

Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes

Xinyu Xu, Yong Gu, Lingling Bian, Yun Shi, Yun Cai, Yang Chen, Heng Chen, Li Qian, Xiangmei Wu, Kuanfeng Xu, Roberto Mallone, Howard W. Davidson, Liping Yu, Jin-Xiong She, Mei Zhang, Tao Yang

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Objective: ZnT8-specific CD8+ T cells in human type 1 diabetes (T1D) have been reported recently, although the results from different laboratories are inconsistent. We aimed to characterize these ZnT8 specific CD8+ T cells and validate assays to screen peptide libraries. Methods: We screened HLA-A2-restricted T cell candidate peptides of ZnT8 with different methods including computer algorithms, MHC-peptide binding and dissociation assays in T2 cell line, identification in HLA-A2 transgenic (Tg) mice and in vivo CTL assays. Then ELISpot assay was used to measure peptide-reactive T cell responses in 49 HLA-A2-restricted T1D patients. Results: We demonstrated that ZnT8_107-116(115), ZnT8_110-118, and ZnT8_177-186 were novel HLA-A*0201-restricted CTL epitopes in T1D patients. ZnT8_107-116(115), ZnT8_115-123, ZnT8_153-161, ZnT8_177-186 and ZnT8_291-300 represent potentially major biomarkers for T1D. T cell responses against these epitopes showed different distributions between recently diagnosed and long-standing patients. Furthermore, they displayed discriminating performance among different ethnicities. We also compared the performance of the epitope identification strategies used herein. The epitopes which exhibited strong immunogenicity in HLA-A2 Tg mice were also well recognized by T1D patients. Conclusions: The differences in autoimmune T cell responses among T1D individuals may open new avenues toward T1D prediction and prevention. It also provides efficient strategies for immune intervention.

Original language	English (US)
Pages (from-to)	854-862
Number of pages	9
Journal	Vaccine
Volume	34
Issue number	6
DOIs	https://doi.org/10.1016/j.vaccine.2015.10.108
State	Published - Feb 3 2016

Keywords

Autoimmune disease
Diabetes
Epitope
T lymphocytes

ASJC Scopus subject areas

Molecular Medicine
Immunology and Microbiology(all)
veterinary(all)
Public Health, Environmental and Occupational Health
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vaccine.2015.10.108

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@article{92c2d05b79f84c4aab4e03ed0dc649a6,

title = "Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes",

abstract = "Objective: ZnT8-specific CD8+ T cells in human type 1 diabetes (T1D) have been reported recently, although the results from different laboratories are inconsistent. We aimed to characterize these ZnT8 specific CD8+ T cells and validate assays to screen peptide libraries. Methods: We screened HLA-A2-restricted T cell candidate peptides of ZnT8 with different methods including computer algorithms, MHC-peptide binding and dissociation assays in T2 cell line, identification in HLA-A2 transgenic (Tg) mice and in vivo CTL assays. Then ELISpot assay was used to measure peptide-reactive T cell responses in 49 HLA-A2-restricted T1D patients. Results: We demonstrated that ZnT8107-116(115), ZnT8110-118, and ZnT8177-186 were novel HLA-A*0201-restricted CTL epitopes in T1D patients. ZnT8107-116(115), ZnT8115-123, ZnT8153-161, ZnT8177-186 and ZnT8291-300 represent potentially major biomarkers for T1D. T cell responses against these epitopes showed different distributions between recently diagnosed and long-standing patients. Furthermore, they displayed discriminating performance among different ethnicities. We also compared the performance of the epitope identification strategies used herein. The epitopes which exhibited strong immunogenicity in HLA-A2 Tg mice were also well recognized by T1D patients. Conclusions: The differences in autoimmune T cell responses among T1D individuals may open new avenues toward T1D prediction and prevention. It also provides efficient strategies for immune intervention.",

keywords = "Autoimmune disease, Diabetes, Epitope, T lymphocytes",

author = "Xinyu Xu and Yong Gu and Lingling Bian and Yun Shi and Yun Cai and Yang Chen and Heng Chen and Li Qian and Xiangmei Wu and Kuanfeng Xu and Roberto Mallone and Davidson, {Howard W.} and Liping Yu and Jin-Xiong She and Mei Zhang and Tao Yang",

note = "Funding Information: We thank Francois A Lemonnier for their contribution to HHDII mice. This work was supported by grants from the National Natural Science Foundation of China 30971405 , 2010CB535008 , 81400808 and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.",

year = "2016",

month = feb,

day = "3",

doi = "10.1016/j.vaccine.2015.10.108",

language = "English (US)",

volume = "34",

pages = "854--862",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier BV",

number = "6",

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TY - JOUR

T1 - Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes

AU - Xu, Xinyu

AU - Gu, Yong

AU - Bian, Lingling

AU - Shi, Yun

AU - Cai, Yun

AU - Chen, Yang

AU - Chen, Heng

AU - Qian, Li

AU - Wu, Xiangmei

AU - Xu, Kuanfeng

AU - Mallone, Roberto

AU - Davidson, Howard W.

AU - Yu, Liping

AU - She, Jin-Xiong

AU - Zhang, Mei

AU - Yang, Tao

N1 - Funding Information: We thank Francois A Lemonnier for their contribution to HHDII mice. This work was supported by grants from the National Natural Science Foundation of China 30971405 , 2010CB535008 , 81400808 and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Publisher Copyright: © 2015 Elsevier Ltd.

PY - 2016/2/3

Y1 - 2016/2/3

N2 - Objective: ZnT8-specific CD8+ T cells in human type 1 diabetes (T1D) have been reported recently, although the results from different laboratories are inconsistent. We aimed to characterize these ZnT8 specific CD8+ T cells and validate assays to screen peptide libraries. Methods: We screened HLA-A2-restricted T cell candidate peptides of ZnT8 with different methods including computer algorithms, MHC-peptide binding and dissociation assays in T2 cell line, identification in HLA-A2 transgenic (Tg) mice and in vivo CTL assays. Then ELISpot assay was used to measure peptide-reactive T cell responses in 49 HLA-A2-restricted T1D patients. Results: We demonstrated that ZnT8107-116(115), ZnT8110-118, and ZnT8177-186 were novel HLA-A*0201-restricted CTL epitopes in T1D patients. ZnT8107-116(115), ZnT8115-123, ZnT8153-161, ZnT8177-186 and ZnT8291-300 represent potentially major biomarkers for T1D. T cell responses against these epitopes showed different distributions between recently diagnosed and long-standing patients. Furthermore, they displayed discriminating performance among different ethnicities. We also compared the performance of the epitope identification strategies used herein. The epitopes which exhibited strong immunogenicity in HLA-A2 Tg mice were also well recognized by T1D patients. Conclusions: The differences in autoimmune T cell responses among T1D individuals may open new avenues toward T1D prediction and prevention. It also provides efficient strategies for immune intervention.

AB - Objective: ZnT8-specific CD8+ T cells in human type 1 diabetes (T1D) have been reported recently, although the results from different laboratories are inconsistent. We aimed to characterize these ZnT8 specific CD8+ T cells and validate assays to screen peptide libraries. Methods: We screened HLA-A2-restricted T cell candidate peptides of ZnT8 with different methods including computer algorithms, MHC-peptide binding and dissociation assays in T2 cell line, identification in HLA-A2 transgenic (Tg) mice and in vivo CTL assays. Then ELISpot assay was used to measure peptide-reactive T cell responses in 49 HLA-A2-restricted T1D patients. Results: We demonstrated that ZnT8107-116(115), ZnT8110-118, and ZnT8177-186 were novel HLA-A*0201-restricted CTL epitopes in T1D patients. ZnT8107-116(115), ZnT8115-123, ZnT8153-161, ZnT8177-186 and ZnT8291-300 represent potentially major biomarkers for T1D. T cell responses against these epitopes showed different distributions between recently diagnosed and long-standing patients. Furthermore, they displayed discriminating performance among different ethnicities. We also compared the performance of the epitope identification strategies used herein. The epitopes which exhibited strong immunogenicity in HLA-A2 Tg mice were also well recognized by T1D patients. Conclusions: The differences in autoimmune T cell responses among T1D individuals may open new avenues toward T1D prediction and prevention. It also provides efficient strategies for immune intervention.

KW - Autoimmune disease

KW - Diabetes

KW - Epitope

KW - T lymphocytes

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JF - Vaccine

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ER -

Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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