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

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
55
2026
2031
Scotto M; Afonso G; Larger E; Raverdy C; Lemonnier FA; Carel JC; Dubois-Laforgue D; Baz B; Levy D; Gautier JF; Launay O; Bruno G; Boitard C; Sechi LA; Hutton JC; Davidson HW; Mallone R.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/106826
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 48
  • ???jsp.display-item.citation.isi??? 43
social impact