Figures & data
Figure 1. Model of citrullination by (A) DC and macrophages, or (B) B cells. (A and B) represent the possible scenarios taking place in APC that result in citrullination of peptide-MHC complexes (pMHC). (A) represents the pathways in DC or macrophages. These cells undergo constitutive autophagy and present the citrullinated peptides after the protein antigen comes into contact with the autophagy vesicles (AV). In (A), the protein antigen lysozyme (HEL) binds to the plasma membrane, and traffics to early endosomal vesicles (EV). From the EV it follows two pathways. In one it is taken to late vesicles (LV), processed to peptides and presented at the cell surface as a pMHC complex. In the second pathway, the protein is taken to an autophagic vesicle (AV) where it is processed to peptides, some of which are citrullinated and presented at the cell surface (cit-pMHC). (B) represents the pathways in B cells. Citrullination in B cells occurs only after autophagy is induced by engagement by antigen of the B cell receptor, shown as an immunoglobulin (Ig) molecule on the cell membrane. Receptor engagement leads to striking subcellular changes that lead to colocalization of AV and antigen-processing compartments, and presentation of citrullinated peptides. (B) shows that the antigen HEL can enter the B cell directly after interaction with plasma membrane, and is taken to EV and LV, to generate unmodified pMHC complexes. However, when HEL is bound to the surface Ig molecules, autophagy is induced, and some of the HEL-Ig complex then traffics to the AV to be processed, and generates the cit-pMHC complex.
