the dynamic processing of cd46 intracellular domains provides a molecular rheostat for t cell activation的动态处理cd46胞内域提供了一个对t细胞活化分子变阻器.pdf

The Dynamic Processing of CD46 Intracellular Domains Provides a Molecular Rheostat for T Cell Activation 1,2 3. 1,2.¤ 4 3 Siobhan Ni Choileain , Nathan J. Weyand , Christian Neumann , Joelle Thomas , Magdalene So , Anne L. Astier1,2* 1 Institute of Immunology and Infection Research, Edinburgh, United Kingdom, 2 Centre for Inflammation Research, Centre for Multiple Sclerosis Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom, 3 BIO5 Institute and Department of Immunobiology, University of Arizona, Tucson, ´ ´ ´ ´ Arizona, United States of America, 4 Universite Lyon 1, Lyon, CNRS, UMR5534, Centre de Genetique Moleculaire et Cellulaire, Villeurbanne, France Abstract Background: Adequate termination of an immune response is as important as the induction of an appropriate response. CD46, a regulator of complement activity, promotes T cell activation and differentiation towards a regulatory Tr1 phenotype. This Tr1 differentiation pathway is defective in patients with MS, asthma and rheumatoid arthritis, underlying its importance in controlling T cell function and the need to understand its regulatory mechanisms. CD46 has two cytoplasmic tails, Cyt1 and Cyt2, derived from alternative splicing, which are co-expressed in all nucleated human cells. The regulation of their expression and precise functions in regulating human T cell activation has not been fully elucidated. Methodology/Principal Findings: Here, we first report the novel role of CD46 in terminating T cell activation. Second, we demo