Abstract: The present invention provides low dose compositions comprising peptides and methods of using the same to treat autoimmune disorders, such as lupus. In particular, the present invention provides low dose compositions comprising nucleosomal histone peptide autoepitopes comprising MHC class I and II binding motifs and methods of using the same to suppress IFN-gamma and/or autoantibody production. In certain embodiments, the compositions contain the histone peptides at subnanomolor concentrations, such as 0.1 nM to 0.9 nM. In other embodiments, the compositions are adminstered in a low dose, such as 5-75 ug of histone peptides per kilogram of patient. In certain embodiments, the present invention provides related diagonstics employing histone peptides.