title: A therapeutic peptide in lupus alters autophagic processes and stability of MHCII molecules in MRL/lpr B cells.
abstract: The P140 phosphopeptide encompassing residues 131-151 of the spliceosomal U1-70K snRNP protein displays protective properties in lupus patients and MRL/lpr mice. It increases peripheral blood lymphocyte apoptosis via a mechanism involving γδ T cells. After intravenous administration, P140 accumulates in the lungs and spleen. It binds both the HSC70/Hsp73 chaperone and MHC class II (MHCII) molecules, which colocalize in splenic MRL/lpr B cells. Expression of HSC70 and MHCII, which is increased in MRL/lpr splenic B cells, is diminished after P140 administration. P140 impairs refolding properties of HSC70 and alters expression of stable MHCII molecules in B lymphocytes. In MRL/lpr B cells, P140 increases the accumulation of the autophagy markers p62/SQSTM1 and LC3-II, consistent with a downregulation of autophagic flux. Our study reveals a very unique property of P140 peptide that alters the autophagy pathway leading to a defect of endogenous (auto)antigen processing in MRL/lpr antigen-presenting B cells and a decrease of T cell priming and signaling.
authors.affiliation: CNRS, Immunologie et Chimie Thérapeutiques, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Page
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gros
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schall
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Briand
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010455:Peptides / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D055550:Protein Stability / Q000187:drug effects
chemical_list: D050883:HSC70 Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D010455:Peptides