less studied HLA-DO suggest that it may work in regulatory fashion on the ability of HLA-DM to choose immunodominant epitopes presented in the thymus. An in vivo study using mice with an HLA-DO knockout lead to an increased disposition for self-reactive immune disease. Research suggests that this may be due to a lack of HLA-DO as a regulator of HLA-DM as a DO knockout leads to less diversity in the MHC II binding as only HLA-DM insensitive peptides will remain bound to the groove. Similarly, HLA-DO is expressed in B cells as well which indicates the possibility of fine tuning the ability of B cells to present a variety of immunodominant epitopes, as opposed to only well fitting peptides unaffected by DM. Structure Before the three-dimensional structure of complexed HLA-DO was elucidated by X-ray crystallography, its crystal structure was modeled after homology studies to classical MHC class II proteins. Following crystallization of the protein, HLA-DO was found to be conformationally similar to classical MHC class II protein, with alterations in the N-terminus. The structure of the free HLA-DO protein, however, remains to be elucidated. References MHC class II