The study of a rare severe combined primary immunodeficiency called the bare lymphocyte syndrome (BLS) led to the identification of class II transactivator (CIITA) and of the three genes coding for the subunits of the heterotrimeric RFX (regulatory factor X-box) complex binding to the X-box in the highly conserved W/SXY module found in all MHC-II gene promoters. The gene discussed is CIITA; the disease is MHC class II deficiency.