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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)854-862
Number of pages9
JournalVaccine
Volume34
Issue number6
DOIs
StatePublished - Feb 3 2016

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HLA-A2 Antigen
insulin-dependent diabetes mellitus
Type 1 Diabetes Mellitus
epitopes
transporters
Epitopes
zinc
immune response
T-lymphocytes
T-Lymphocytes
assays
peptides
Transgenic Mice
genetically modified organisms
peptide libraries
Peptide T
Peptide Library
mice
nationalities and ethnic groups
zinc-binding protein

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

Cite this

Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes. / Xu, Xinyu; Gu, Yong; Bian, Lingling; Shi, Yun; Cai, Yun; Chen, Yang; Chen, Heng; Qian, Li; Wu, Xiangmei; Xu, Kuanfeng; Mallone, Roberto; Davidson, Howard W.; Yu, Liping; She, Jin-Xiong; Zhang, Mei; Yang, Tao.

In: Vaccine, Vol. 34, No. 6, 03.02.2016, p. 854-862.

Research output: Contribution to journalArticle

Xu, X, Gu, Y, Bian, L, Shi, Y, Cai, Y, Chen, Y, Chen, H, Qian, L, Wu, X, Xu, K, Mallone, R, Davidson, HW, Yu, L, She, J-X, Zhang, M & Yang, T 2016, 'Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes', Vaccine, vol. 34, no. 6, pp. 854-862. https://doi.org/10.1016/j.vaccine.2015.10.108
Xu, Xinyu ; Gu, Yong ; Bian, Lingling ; Shi, Yun ; Cai, Yun ; Chen, Yang ; Chen, Heng ; Qian, Li ; Wu, Xiangmei ; Xu, Kuanfeng ; Mallone, Roberto ; Davidson, Howard W. ; Yu, Liping ; She, Jin-Xiong ; Zhang, Mei ; Yang, Tao. / Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes. In: Vaccine. 2016 ; Vol. 34, No. 6. pp. 854-862.
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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.",
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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

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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