Evidence that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin superfamily

Central T-cell tolerance of neurondocrine functions has been proposed to be primarily induced by the thymic repertoire of neuroendocrine self antigens. The present study aimed at characterizing the human thymic insulin-related self antigen able to represent the pancreatic islet ß cell function in face of the developing T cells. Immunofluorescence studies were performed on human and rat thymic sections, as wess as on the rat IT-45R1 thymic epithelial cell line using several antibodies to epitopes of the insulin peptide family. These studies identify beyond any doubt that IGF2 is the dominant thymic peptide of the insulin family. The sequence of an insulin-derived autoantigen is proposed. This autoantigen is a nonamer and has a hydrophobic residue leucine at position 9. In human species, this autoantigen would primarily be tolerogenic for the pancreatic ß-cell endocrine function during fetal development.