Epitopes described in "Zinc transporter (ZnT)8(186-194) is an immunodominant CD8+ T cell epitope in HLA-A2+ type 1 diabetic patients."

Article Authors:M Scotto; G Afonso; E Larger; C Raverdy; F A Lemonnier; J C Carel; D Dubois-Laforgue; B Baz; D Levy; J F Gautier; O Launay; G Bruno; C Boitard; L A Sechi; J C Hutton; H W Davidson; R Mallone
Article Title:Zinc transporter (ZnT)8(186-194) is an immunodominant CD8+ T cell epitope in HLA-A2+ type 1 diabetic patients.
Reference Detail
Reference ID:1024967
Abstract:AIMS/HYPOTHESIS: Anti-zinc transporter (ZnT)8 autoantibodies are commonly detected in type 1 diabetic patients. We hypothesised that ZnT8 is also recognised by CD8(+) T cells and aimed to identify HLA-A2 (A*02:01)-restricted epitope targets. METHODS: Candidate epitopes were selected by ZnT8 plasmid DNA immunisation of HLA-A2/DQ8 transgenic mice and tested for T cell recognition in peripheral blood mononuclear cells of type 1 diabetic, type 2 diabetic and healthy participants by IFN- enzyme-linked immunospot. RESULTS: White HLA-A2(+) adults (83%) and children (60%) with type 1 diabetes displayed ZnT8-reactive CD8(+) T cells that recognised a single ZnT8(186-194) (VAANIVLTV) epitope. This ZnT8(186-194)-reactive fraction accounted for 50% to 53% of total ZnT8-specific CD8(+) T cells. Another sequence, ZnT8(153-161) (VVTGVLVYL), was recognised in 20% and 25% of type 1 diabetic adults and children, respectively. Both epitopes were type 1 diabetes-specific, being marginally recognised by type 2 diabetic and healthy participants (7-12% for ZnT8(186-194), 0% for ZnT8(153-161)). CONCLUSIONS/INTERPRETATION: ZnT8-reactive CD8(+) T cells are predominantly directed against the ZnT8(186-194) epitope and are detected in a majority of type 1 diabetic patients. The exceptional immunodominance of ZnT8(186-194) may point to common environmental triggers precipitating beta cell autoimmunity.
Affiliations:Inserm, U986, DeAR Lab Avenir, Saint Vincent de Paul Hospital, 82 avenue Denfert Rochereau, 75674 Paris Cedex 14, France.
Reference Type:Literature
PubMed ID:22526607
Journal Volume:55
Article Pages:2026-31
Journal ISSN:0012-186X
Article Chemical List:Autoantibodies;Cation Transport Proteins;Epitopes, T-Lymphocyte;HLA-A2 Antigen;SLC30A8 protein, human
Article MeSH List:Adolescent; Adult; Animals; Autoantibodies(genetics); CD4-Positive T-Lymphocytes(immunology); CD8-Positive T-Lymphocytes(immunology); Cation Transport Proteins(genetics; immunology); Child; Child, Preschool; Diabetes Mellitus, Type 1(genetics; immunology); Epitope Mapping; Epitopes, T-Lymphocyte(genetics; immunology); Female; HLA-A2 Antigen(genetics; immunology); Humans; Infant; Male; Mice; Mice, Transgenic; Middle Aged
Curation Last Updated:2016-04-02 20:03:15