The love and hate relationship of HLA-DM/DO in the selection of immunodominant epitopes

Successful activation of CD4 T cells is centered around the ability of antigen presenting cells to successfully process, select Class II immunodominant epitopes from exogenous antigens and to present it to cognate T cells. To achieve this, newly synthesized MHC-II molecules are transferred to a specialized compartment which contain both exogenous antigens and the Class II processing machinery. Here in a process known as ‘editing,’ the Class II accessory molecule DM (HLA-DM human; murine H2-M) facilitates the loading and selection of exogenous peptides to MHC class II molecules thereby assuring proper selection of immunodominant epitopes. A second Class II accessory molecule, DO (HLA-DO human; murine H2-O), mainly present in B cells and thymic epithelium also contributes to the selection of immunodominant epitopes. Yet, despite a wealth of mechanistic insights into how DM functions, understanding the contributions of DO to epitope selection has proven to be highly challenging. In this review, we have attempted to discuss published in vitro and in vivo data during the past three years with insights into the biology of DO.