Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes-associated human MHC class II allele, DRB1*0401

The Journal of Clinical Investigation
L S WickerP J Whiteley

Abstract

The identification of class II binding peptide epitopes from autoimmune disease-related antigens is an essential step in the development of antigen-specific immune modulation therapy. In the case of type 1 diabetes, T cell and B cell reactivity to the autoantigen glutamic acid decarboxylase 65 (GAD65) is associated with disease development in humans and in nonobese diabetic (NOD) mice. In this study, we identify two DRB1*0401-restricted T cell epitopes from human GAD65, 274-286, and 115-127. Both peptides are immunogenic in transgenic mice expressing functional DRB1*0401 MHC class II molecules but not in nontransgenic littermates. Processing of GAD65 by antigen presenting cells (APC) resulted in the formation of DRB1*0401 complexes loaded with either the 274-286 or 115-127 epitopes, suggesting that these naturally derived epitopes may be displayed on APC recruited into pancreatic islets. The presentation of these two T cell epitopes in the islets of DRB1*0401 individuals who are at risk for type 1 diabetes may allow for antigen-specific recruitment of regulatory cells to the islets following peptide immunization.

References

Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A E KarlsenD Foster
Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·R Tampé, H M McConnell
Nov 24, 1994·The New England Journal of Medicine·M A Atkinson, N K Maclaren
Jul 1, 1994·The Journal of Experimental Medicine·A WoodsD M Zaller
Sep 1, 1994·International Archives of Allergy and Immunology·J B RothbardD Zaller
Oct 19, 1993·Biochimica Et Biophysica Acta·D S LeeD L Kaufman

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Citations

Mar 10, 2001·Diabetes/metabolism Research and Reviews·Y Park, G S Eisenbarth
Feb 26, 2004·Journal of Immunological Methods·Jean-Marie FourneauPeter M van Endert
Oct 3, 1999·Veterinary Immunology and Immunopathology·G M HappL Fox
Oct 3, 1998·Human Immunology·D OuA J Tingle
Apr 1, 2004·Endocrinology and Metabolism Clinics of North America·Timothy I M Tree, Mark Peakman
Jan 23, 1999·Current Opinion in Immunology·S L ParryG Sønderstrup
Jan 13, 2000·Current Opinion in Immunology·F S Wong, C A Janeway
Mar 11, 2000·Current Opinion in Immunology·A Sette, G T Nepom
Feb 19, 2000·Current Opinion in Immunology·R S Abraham, C S David
Feb 14, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Gerald T Nepom
Feb 3, 2005·Nature Reviews. Drug Discovery·Peter J Bugelski
Jan 9, 2013·Nature Reviews. Endocrinology·Ake Lernmark, Helena Elding Larsson
Mar 8, 2002·Clinical and Experimental Immunology·R J Boyton, D M Altmann
Oct 24, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shuji MatsumuraM Eric Gershwin
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·S D PatelG Sonderstrup-McDevitt
Jul 28, 2001·Diabetes Technology & Therapeutics·W HaoA Lernmark
Jan 4, 2007·Thyroid : Official Journal of the American Thyroid Association·Pavel PichurinSandra M McLachlan
Oct 31, 1998·Immunological Reviews·J F BachP M van Endert
Aug 18, 1999·Immunological Reviews·V Taneja, C S David
Apr 4, 2001·The Journal of Clinical Investigation·L WenF S Wong
Apr 16, 1998·The Journal of Clinical Investigation·V Taneja, C S David
Dec 10, 1999·The Journal of Clinical Investigation·A Lernmark
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·A GelukT H Ottenhoff
Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·G T NepomB S Nepom
Nov 28, 2012·La Presse médicale·Christian Boitard
Jun 3, 2008·Journal of Autoimmunity·Gustavo Fenalti, Merrill J Rowley
Nov 1, 2003·Annals of the New York Academy of Sciences·Tobias LohmannR David G Leslie

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