Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion

• Autores: Thomas Delong, Timothy A. Wiles, Rocky L. Baker, Brenda Bradley
• Localización: Science, ISSN 0036-8075, Vol. 351, Nº 6274, 2016, págs. 711-714
• Idioma: inglés
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• Resumen

  • T cell–mediated destruction of insulin-producing β cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in β cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in β cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in β cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D.