ZnT8 is a major CD8+ T cell-recognized autoantigen in pediatric type 1 diabetes.

Diabetes
Émmanuelle ÉnéePeter van Endert

Abstract

Type 1 diabetes results from the destruction of β-cells by an autoimmune T-cell response assisted by antigen-presenting B cells producing autoantibodies. CD8(+) T-cell responses against islet cell antigens, thought to play a central role in diabetes pathogenesis, can be monitored using enzyme-linked immunosorbent spot (ELISpot) assays. However, such assays have been applied to monitoring of adult patients only, leaving aside the large and increasing pediatric patient population. The objective of this study was twofold: 1) to develop a CD8(+) T-cell interferon-γ ELISpot assay for pediatric patients and 2) to determine whether zinc transporter 8 (ZnT8), a recently described target of autoantibodies in a majority of patients, is also recognized by autoreactive CD8(+) T cells. Using DNA immunization of humanized mice, we identified nine HLA-A2-restricted ZnT8 epitopes. Among 36 HLA-A2(+) children with diabetes, 29 responded to ZnT8 epitopes, whereas only 3 of 16 HLA-A2(+) control patients and 0 of 17 HLA-A2(-) control patients responded. Some single ZnT8 epitopes performed as well as the group of epitopes in discriminating between patients and control individuals. Thus, ZnT8 is a major CD8(+) T-cell autoantigen, and ELISpot assays ...Continue Reading

References

Dec 1, 1992·The Journal of Clinical Investigation·S Caillat-ZucmanJ F Bach
Dec 22, 1999·Immunogenetics·H RammenseeS Stevanović
May 6, 2003·European Journal of Immunology·John A GebeGerald T Nepom
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshiyuki TakakiDavid V Serreze
Jan 24, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carmen P WongRoland Tisch
Mar 1, 2007·Diabetes·Roberto MallonePeter van Endert
Mar 23, 2007·Annals of the New York Academy of Sciences·David V SerrezeTeresa P Dilorenzo
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Philippe BlancouJean-Marie Bach
Oct 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Janet M WenzlauJohn C Hutton
Feb 5, 2008·Journal of Immunological Methods·Emanuela MartinuzziRoberto Mallone
Mar 8, 2008·The Journal of Clinical Investigation·Godwin NchindaRalph M Steinman
Apr 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emmanuelle EnéePeter van Endert
Apr 9, 2009·Nature Reviews. Endocrinology·Décio L EizirikFernanda Ortis
Oct 7, 2009·The Review of Diabetic Studies : RDS·Ken T Coppieters, Matthias G von Herrath
Apr 24, 2010·Immunity·Brian StadinskiGeorge S Eisenbarth
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Roland KratzerPeter van Endert
Nov 3, 2010·Immunology·Jeffrey BabadTeresa P DiLorenzo
Apr 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·MyLinh DangHoward W Davidson
Nov 5, 2011·Current Opinion in Immunology·Bart O Roep, Mark Peakman
Jan 4, 2012·The Journal of Experimental Medicine·Ken T CoppietersMatthias G von Herrath

❮ Previous
Next ❯

Citations

Jan 5, 2013·Nutrition Research Reviews·Fabrice Chimienti
Mar 3, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Yannick F FuchsEzio Bonifacio
May 11, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Yi LiLi Wang
Nov 13, 2014·Diabetic Medicine : a Journal of the British Diabetic Association·V L RudlandG P Ross
Oct 22, 2014·Immunology·Gayatri MukherjeeTeresa P DiLorenzo
Jun 6, 2013·Clinical Endocrinology·Sarah Côté-BigrasDiane Rottembourg
May 29, 2015·Science Translational Medicine·Mahzad AkbarpourMaria Grazia Roncarolo
Jul 13, 2013·Diabetes Care·Amy K MottlUNKNOWN SEARCH for Diabetes in Youth Study Group
Jun 20, 2016·Journal of Autoimmunity·Yamina HamelPeter van Endert
Aug 8, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hideki OguraKevan C Herold
May 10, 2016·F1000Research·François-Xavier MauvaisPeter van Endert
Aug 2, 2017·The Journal of Clinical Investigation·Alberto Pugliese
Aug 25, 2019·Diabetologia·Claire L Williams, Anna E Long
Jun 18, 2014·The Journal of Clinical Endocrinology and Metabolism·Hironori BandoYutaka Takahashi
Dec 1, 2017·The Journal of Biological Chemistry·Chengfeng MerrimanDax Fu
Dec 21, 2017·Frontiers in Endocrinology·Adam L BurrackBrian T Fife
Sep 1, 2018·Frontiers in Immunology·Charles J KrogerRoland M Tisch

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Methods Mentioned

BETA
enzyme-linked immunosorbent spot
PCR
FCS

Software Mentioned

GraphPad Prism

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