Identification and modulation of a naturally processed T cell epitope from the diabetes- associated autoantigen human glutamic acid decarboxylase 65 (hGAD65)

摘要

T cell recognition of autoantigens is critical to progressive immune- mediated destruction of islet cells. which leads to autoimmune diabetes. We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65). by using a combination of chromatography and mass spectrometry of peptides bound by the type Ⅰ diabetes (insulin- dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. Peptides encompassing this epitope-stimulated GAD65-specific T cells from diabetic patients and a DR4-positive individual at high risk for developing IDDM. T cell responses were antagonized by altered peptide ligands containing single amino acid modifications. This direct identification and manipulation of GAD65 epitope recognition provides an approach toward dissection of the com- plex CD4~+ T cell response in IDDM.