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Zinc transporter (ZnT)8(186-194) is an immunodominant CD8+ T cell epitope in HLA-A2+ type 1 diabetic patients.
Scotto, M; Afonso, G; Larger, E; Raverdy, C; Lemonnier, F A; Carel, J C; Dubois-Laforgue, D; Baz, B; Levy, D; Gautier, J F; Launay, O; Bruno, G; Boitard, C; Sechi, L A; Hutton, J C; Davidson, H W; Mallone, R.
Afiliação
  • Scotto M; Inserm, U986, DeAR Lab Avenir, Saint Vincent de Paul Hospital, 82 avenue Denfert Rochereau, 75674 Paris Cedex 14, France.
Diabetologia ; 55(7): 2026-31, 2012 Jul.
Article em En | MEDLINE | ID: mdl-22526607
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-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 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígeno HLA-A2 / Linfócitos T CD8-Positivos / Epitopos de Linfócito T / Proteínas de Transporte de Cátions / Diabetes Mellitus Tipo 1 Limite: Adolescent / Adult / Animals / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Idioma: En Revista: Diabetologia Ano de publicação: 2012 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígeno HLA-A2 / Linfócitos T CD8-Positivos / Epitopos de Linfócito T / Proteínas de Transporte de Cátions / Diabetes Mellitus Tipo 1 Limite: Adolescent / Adult / Animals / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Idioma: En Revista: Diabetologia Ano de publicação: 2012 Tipo de documento: Article País de afiliação: França