This prominent role of CIITA in the homeostasis of the immune system has emerged from the elucidation of the molecular defect at the basis of the bare lymphocyte syndrome (BLS), a severe form of combined immunodeficiency, characterized by the loss of expression of MHC-II molecules (Yang et al., 1988; Steimle et al., 1993; Reith and Mach, 2001). The gene discussed is CIITA; the disease is MHC class II deficiency.