Evidence for recognition of novel islet T cell antigens by granule-specific T cell lines from new onset type 1 diabetic patients.

摘要: Type 1 diabetes is a T cell-mediated autoimmune disease where number of islet β-cell target autoantigens have been characterized on the basis reactivity with autoantibodies. Nevertheless, there remains uncertainty nature another group associated secretory granule fraction β-cells that appear to be targeted predominantly by autoreactive cells. We previously CD4+, HLA-DR-restricted cell lines from new onset type diabetic patients are specific for rat tumour insulinoma, RIN. The line first patient, HS, proliferates in response crude microsomal membranes prepared recently established, pure human NES2Y. In addition, HS also responds fractions murine insulinoma grown RIP-Tag mice, showing recognition species-conserved antigen(s) β-cells. Using partially matched antigen-presenting cells, cells and derived second MR, were shown restricted disease-associated DRB1*0101 DRB1*0404 alleles, respectively. Neither or MR proliferate large panel candidate antigens, including insulin, proinsulin, glutamic acid decarboxylase, protein tyrosine phosphatase IA-2/phogrin, imogen-38, ICA69 hsp60. Our data provide compelling evidence presence antigens recognized lines, whose definition may contribute our knowledge induction as well diagnosis.