Presentation of citrullinated peptides by class II histocompatibility molecules is associated with autophagy. (100.19)

Abstract

Abstract Autoimmune responses to citrullinated proteins are associated with rheumatoid arthritis; however, little is known of the mechanism of citrullination by the antigen presenting cells (APC) of the immune system. Using T cell hybridomas as probes, we found constitutive presentation by class II-Major Histocompatibility Complex (MHC) molecules of a dominant citrullinated peptide from hen egg-white lysozyme (HEL) by either macrophages or dendritic cells. Treatment of APC with 3-Methyladenine (3MA) blocked presentation of the citrullinated peptides after processing unmodified HEL, but presentation of unmodified peptides was not at all affected. In contrast presentation of citrullinated peptides by splenic B cells or B lymphoma cells was not detected under normal culture conditions. However, B cell lines presented citrullinated peptides after serum starvation in a process affected by 3MA treatment or by reducing the expression of the autophagy protein Atg5. Higher levels of citrulline in naturally processed peptides from serum starved B cell lines were detected biochemically. Primary B cells presented citrullinated HEL peptides after engagement of their B cell receptor by antigen or by using anti-immunoglobulin antibodies. Our findings demonstrate a role for autophagy in citrullination of antigen during processing by APC and indicate a link in B cells between engagement of their antigen receptor and presentation of citrullinated peptides.