Peptide (antigen) binding to major histocompatibility complex (MHC) class II molecules destined for presentation to CD4+ helper T cells is determined by two key events. These include the dissociation of class II-associated invariant chain peptides (CLIP) from an antigen binding groove in MHC II-Ig dimers and by the activity of MHC molecules HLA-DM and -DO. Accumulating in endosomal/lysosomal compartments and on the surface of B cells, HLA-DM, -DO molecules regulate the dissociation of CLIP and the subsequent binding of exogenous peptides to HLA class II molecules (HLA-DR) by sustaining a conformation that favors peptide exchange. RFLP analysis of HLA-DM genes from rheumatoid arthritis (RA) patients suggests that certain polymorphisms are genetic factors for RA susceptibility.
HLA class II histocompatibility antigen, DO beta chain; HLA-DO beta; MHC class II antigen DOB