The availability, of “humanized” mice [HLA-transgenic (Tg) mice] that were genetically manipulated to express either of the human DRB1*15:01, DQA1*01:02-DQB1*06:02, or DRB5*01:01 molecules, provide a powerful tool to discern the potential contribution of each of these three sets of genes, individually or in combination (epistasis), to the development of MS. Here, HLA-DRB5 is linked to myeloid sarcoma.