The convergent roles of tapasin and HLA-DM in antigen presentation

Cytotoxic and helper T cells respond to peptides derived from endogenous and exogenous sources that bind to major histocompatibility complex (MHC) class I and class II molecules and are presented on antigen-presenting cells. MHC class I and class II structures and maturation pathways have evolved to optimize antigen presentation to their respective T cells. The accessory proteins tapasin and HLA-DM (DM) crucially influence the selection of peptides that bind to the MHC molecules. We discuss here the dynamic interactions of tapasin and DM with their corresponding MHC molecules that indicate striking parallels. Utilization of a common mode of peptide selection by two different, but related, biological systems argue for its mechanistic validity.