A Therapeutic Peptide In Lupus Alters Autophagic Processes And Stability Of Mhcii Molecules In Mrl/Ipr B Cells

The P140 phosphopeptide encompassing residues 131-151 of the spliceosomal U1-70K snRNP protein displays protective properties in lupus patients and MRL/1pr mice. It increases peripheral blood lymphocyte apoptosis via a mechanism involving gamma delta 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/Ipr B cells. Expression of HSC70 and MHCII, which is increased in MRL/1pr 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/Ipr 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/Ipr antigen-presenting B cells and a decrease of T cell priming and signaling.