Oral Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Immunodominant antigen targets in T1D: pathophysiological basis and therapeutic opportunities (#46)

Slobodan Culina 1 , Georgia Afonso 1 , Matthieu Scotto 1 , Nimesh Gupta 2 , Thomas Osterbye 3 , Victor Appay 4 , F. Susan Wong 5 , Sebastien Lacroix-Desmazes 2 , Roberto Mallone 1
  1. Cochin Institute, DeAR Lab Avenir, INSERM U1016, Paris, France
  2. INSERM UMRS 872, Centre de Recherche des Cordeliers, Paris, France
  3. Panum Institute, Copenhagen, Denmark
  4. INSERM UMRS 945 , Université Pierre et Marie Curie, Paris, France
  5. Cardiff University, Cardiff, UK

The cartography of β-cell epitopes recognized by autoreactive CD8+ T cells has revealed the wide heterogeneity of the autoimmune targets recognized in different T1D patients. We recently described a HLA-A2-restricted ZnT8 epitope which emerged as a notable exception, being recognized in 73% of new-onset T1D patients, both adults and children. Potential reasons for this exceptional immunodominance have been investigated and may reside in inefficient negative selection in the thymus and cross-reactivity with homologous epitopes derived from common infectious agents. Such immunodominant epitopes may offer novel therapeutic opportunities as more universal vaccinal agents that may be delivered to the thymus to boost defective central tolerance. Vaccination strategies targeting this first thymic check point during fetal and neonatal life have been tested in mouse models and shown to confer T1D protection.