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T Cell Response to Preproinsulin I and II in the Nonobese Diabetic Mouse¹

Philippe Halbout^*, Jean-Paul Briand, Chantal Bécourt^*, Sylviane Muller and Christian Boitard^2,*

^* Institut National de la Santé et de la Recherche Médicale Unité 561, Hôpital Cochin-Saint Vincent de Paul, Paris, France; and Centre National de la Recherche Scientifique-Unité Propre de Recherche 9021, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France

Immunization against insulin, insulin B chain, or B chain peptide B_9–23 (preproinsulin peptide II_33–47) prevents diabetes in the nonobese diabetic (NOD) mouse. Whether or not peptide II_33–47 is the only proinsulin determinant recognized by CD4 T cells remains unclear. Using two peptide libraries spanning the entire sequence of preproinsulin I and preproinsulin II, respectively, we identified T cells specific for four proinsulin epitopes within the islet cell infiltrate of prediabetic female NOD mice. These epitopes were among immunogenic epitopes to which a T cell response was detected after immunization of NOD mice with individual peptides in CFA. Immunogenic epitopes were found on both isoforms of insulin, especially proinsulin II, which is the isoform expressed in the thymus. The autoimmune response to proinsulin represented only part of the immune response to islet cells within the islet cell infiltrate in 15-wk-old NOD mice. This is the first systematic study of preproinsulin T cell epitopes in the NOD mouse model.

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