regulation of cathepsin g reduces the activation of proinsulin-reactive t cells from type 1 diabetes patients的监管组织蛋白酶g降低proinsulin-reactive t细胞的活化与1型糖尿病患者.pdfVIP

Regulation of Cathepsin G Reduces the Activation of Proinsulin-Reactive T Cells from Type 1 Diabetes Patients 1 ¨ 1 1 ¨ 1 2¤ 3 Fang Zou , Nadja Schafer , David Palesch , Ruth Brucken , Alexander Beck , Marcin Sienczyk , Hubert 4 5 1 1 Kalbacher , ZiLin Sun , Bernhard O. Boehm , Timo Burster * ¨ 1 Division of Endocrinology and Diabetes, Center for Internal Medicine, University Medical Center Ulm, Ulm, Germany, 2 Panatecs, Tubingen, Germany, 3 Wroclaw ¨ ¨ University of Technology, Wroclaw, Poland, 4 Medical and Natural Sciences Research Center, University of Tubingen, Tubingen, Germany, 5 Institute of Diabetes, Zhongda Hospital Medical School, Southeast University, Nanjing, China Abstract Autoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 diabetes mellitus (T1D). Self-proteins can be processed by cathepsins (Cats) within endocytic compartments and loaded to major histocompatibility complex (MHC) class II molecules for CD4+ T cell inspection. However, the processing and presentation of proinsulin by antigen-presenting cells (APC) in humans is only partially understood. Here we demonstrate that the processing of proinsulin by B cell or myeloid dendritic cell (mDC1)-derived lysosomal cathepsins resulted in several proinsulin-derived intermediates. These intermediates were similar to those