Taken together, by showing different impact of vitamin D on the CNS pathology and peripheral immune response during EAE in DA.PVGav1-Vra4 congenic rats compared to the parental strains, our data emphasize relevance of naturally occurring allelic differences in the Vra4 locus/Mhc2ta for efficacy of vitamin D in modulation of MS-like neuroinflammation, and potentially even MS. This evidence concerns the gene CIITA and myeloid sarcoma.