T cells to a dominant epitope of GAD65 express a public CDR3 motif

International Immunology
Anthony QuinnE E Sercarz

Abstract

Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes, and serve as a model for type 1 diabetes (T1D) and natural autoimmunity. T cell responses to the pancreatic islet antigen glutamic acid decarboxylase 65 (GAD65) can be detected in the spleens of young prediabetic NOD mice, which display a unique MHC class II molecule. Here, we report that a distinct TcR beta chain and CDR3 motif are utilized by all NOD mice in response to a dominant determinant on GAD65, establishing a public repertoire in the spontaneous autoimmunity to an important islet cell antigen. GAD65 530-543 (p530)-reactive T cells preferentially utilize the Vbeta4, Dbeta2.1 and Jbeta2.7 gene segments, with a CDR3 that is characterized by a triad of amino acids, DWG, preceded by a polar residue. In addition, we used CDR3 length spectratyping, CDR3-specific reverse transcriptase-PCR and direct TcR sequencing to show that the TcR beta chain structural patterns associated with p530-specific T cells consistently appeared in the islets of young NOD mice with insulitis, but not in the inflamed islets of streptozotocin-treated C57BL/6 mice, or in inflamed NOD salivary glands. To our knowledge, this is the first report to demonstrate that a public T cell ...Continue Reading

References

Feb 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T M HaqqiC S David
Sep 1, 1991·The Journal of Experimental Medicine·J A ShizuruC G Fathman
Jun 1, 1991·Clinical Immunology and Immunopathology·E GoillotJ L Touraine
Jul 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·S CandéiasK Haskins
May 1, 1988·The Journal of Experimental Medicine·S S ZamvilH Acha-Orbea
Jun 11, 1981·The New England Journal of Medicine·G F Cahill, H O McDevitt
Jan 1, 1995·Annual Review of Immunology·L S WickerL B Peterson
Dec 1, 1994·Journal of Autoimmunity·D R WegmannD Daniel
May 3, 1996·Cell·R Tisch, H McDevitt
Feb 1, 1996·Immunity·Y YangC G Fathman
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·M A LipesA M Davalli
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·E SimoneG S Eisenbarth
Jun 1, 1997·Journal of Autoimmunity·L S GazdaK J Lafferty
Feb 14, 1998·The Journal of Clinical Investigation·D ZekzerR S Sherwin
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·L GengA C Hayday
May 20, 1999·Journal of Autoimmunity·S M Dilts, K J Lafferty
Jun 5, 1999·Journal of Immunological Methods·M KurokawaT Kato
Oct 21, 2000·Journal of Autoimmunity·J W YoonH S Jun
Feb 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A QuinnE E Sercarz
Apr 4, 2001·The Journal of Clinical Investigation·G Sønderstrup, H O McDevitt
Jun 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S S WilsonD DeLuca
Jul 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A QuinnE E Sercarz

❮ Previous
Next ❯

Citations

Feb 12, 2009·Mammalian Genome : Official Journal of the International Mammalian Genome Society·John P MordesElizabeth P Blankenhorn
Feb 9, 2011·Immunology and Cell Biology·John J MilesDavid A Price
Feb 27, 2008·International Reviews of Immunology·Raghavan Raju, Christiane S Hampe
Jan 31, 2012·Cellular Immunology·Emanual Maverakis
Dec 19, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Rhea Y BusickAnthony Quinn
Mar 23, 2007·Annals of the New York Academy of Sciences·Elizabeth P BlankenhornJohn P Mordes
Nov 19, 2013·Journal of Immunological Methods·Anne EugsterEzio Bonifacio
Jan 9, 2014·Journal of Autoimmunity·Mariapaola MarinoEmanuela Bartoccioni
May 28, 2011·Diabetes·Sarah S RascheAnthony Quinn
Jan 8, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna L FurmanskiJulian Dyson
Aug 28, 2020·Frontiers in Endocrinology·David Perna-BarrullMarta Vives-Pi
Feb 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne EugsterEzio Bonifacio

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.