Identification of novel HLA-A 0201-restricted cytotoxic T lymphocyte epitopes from Zinc Transporter 8

Numerous evidences demonstrated that type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, and CD8(+) T cells play an important role in the development of T1D. Zinc Transporter 8 (ZnT8) has emerged in recent years as a target of disease-associated autoreactive T cells in huma...

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Bibliographic Details
Published in:Vaccine 2013-03, Vol.31 (12), p.1610-1615
Main Authors: Li, Shufa, Li, Haiying, Chen, Bing, Lu, Debin, Deng, Wuquan, Jiang, Youzhao, Zhou, Zhongqi, Yang, Zhao
Format: Article
Language:English
Subjects:
Animals
Cation Transport Proteins - immunology
CD8-Positive T-Lymphocytes - immunology
Cell Line
Diabetes Mellitus, Type 1 - immunology
Epitope Mapping
Epitopes, T-Lymphocyte - immunology
HLA-A2 Antigen - immunology
Humans
Mice
Mice, Transgenic
Peptides - chemical synthesis
Peptides - immunology
Zinc Transporter 8
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Summary:Numerous evidences demonstrated that type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, and CD8(+) T cells play an important role in the development of T1D. Zinc Transporter 8 (ZnT8) has emerged in recent years as a target of disease-associated autoreactive T cells in human T1D. However, ZnT8-associated CTL specific-peptides have not been identified. In this study, we predicted and identified HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) epitopes derived from ZnT8, and utilized it to immunize HLA-A2.1/Kb transgenic (Tg) mice. The results demonstrated that peptides of ZnT8 containing residues 107-115, 115-123 and 145-153 could elicit specific CTLs in vitro, and induce diabetes in mice. The results suggest that these specific peptides are novel HLA-A*0201-restricted CTL epitopes, and could have therapeutic potential in preventing of T1D disease.
ISSN:1873-2518
DOI:10.1016/j.vaccine.2012.12.008