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+ Tcells 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-γ 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 ZnT8186-194 (VAANIVLTV) epiTope. This ZnT8186-194-reactive fraction accounted for 50% to 53% of total ZnT8-specific CD8+ T cells. Another sequence, ZnT8153-161 (VVTGVLVYL), was recognised in
Zinc transporter (ZnT)8(186-194) is an immunodominant CD8 (+) T cell epitope in HLA-A2 (+) type 1 diabetic patients.
BRUNO, Graziella;
2012-01-01
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+ Tcells 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-γ 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 ZnT8186-194 (VAANIVLTV) epiTope. This ZnT8186-194-reactive fraction accounted for 50% to 53% of total ZnT8-specific CD8+ T cells. Another sequence, ZnT8153-161 (VVTGVLVYL), was recognised in
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
