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SUMMARY:Autoreactive CD4 T Cells and their Antigens in Type 1 Diabetes - P
 rofessor Katie Haskins\, University of Colorado\, Denver
DTSTART:20120425T113000Z
DTEND:20120425T123000Z
UID:TALK37357@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:CD4 T cells reactive with beta-cell antigens play a key role i
 n the pathogenesis and regulation of  type 1 diabetes (T1D).  With the exc
 eption of insulin\, however\, little is known of the antigens that drive C
 D4 T cells.  \n\nWe have recently described two new autoantigens for diabe
 togenic CD4 T cells.  Chromogranin A (ChgA) and islet amyloid polypeptide 
 (IAPP) are both secretory proteins\, and like insulin\, are proteolyticall
 y cleaved within beta granules to generate active peptides.  Under conditi
 ons of cellular stress\, which are common to inflammatory states\, peptide
 s secreted from the beta granules may undergo modification\, a process tha
 t can lead to neo-antigens.  \n\nOur data indicate that antigenicity of a 
 T cell ligand from ChgA is greatly enhanced through enzymatic modification
 \, suggesting that peptide ligands seen by autoreactive T cells in T1D may
  be products of post-translational modification. We have also identified a
 n antigenic epitope from IAPP and this peptide has been used to develop a 
 new tetramer reagent that can be used to track IAPP-reactive T cells.  \n\
 nNew data indicate that both IAPP and ChgA-reactive T cells can be found i
 n pre-diabetic NOD mice.  Ligands from these two proteins are also being t
 ested in antigen-specific tolerance induction strategies.\n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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