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

, : Zinc transporter (ZnT)8(186-194) is an immunodominant CD8+ T cell epitope in HLA-A2+ type 1 diabetic patients. Diabetologia 55(7): 2026-2031

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*2:1)-restricted epitope targets. 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. White HLA-A2+ adults (83%) and children (6%) with type 1 diabetes displayed ZnT8-reactive CD8+ T cells that recognised a single ZnT8186 194 (VAANIVLTV) epitope. This ZnT8186 194-reactive fraction accounted for 5% to 53% of total ZnT8-specific CD8+ T cells. Another sequence, ZnT8153 161 (VVTGVLVYL), was recognised in 2% 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 ZnT8186 194, % for ZnT8153 161). Conclusions/interpretation ZnT8-reactive CD8+ T cells are predominantly directed against the ZnT8186 194 epitope and are detected in a majority of type 1 diabetic patients. The exceptional immunodominance of ZnT8186 194 may point to common environmental triggers precipitating beta cell autoimmunity.


PMID: 22526607

DOI: 10.1007/s00125-012-2543-z

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