The initiation of an immune response requires that a foreign antigen be degraded, and that one of the degradative fragments be presented in the context of a human leukocyte antigen (HLA) class II molecule to an antigen-specific helper T cell. The success of this process is maximized by the diversity of the class II molecules possessed by a given person. The expression of the HLA class II molecules is highly selective. Aberrant expression has been postulated to be responsible for autoimmune disease. The interaction of inducible tissue-specific transacting factors with cis-acting genetic elements adjacent to the coding portion of the class II genes is responsible for both normal and aberrant expression of class II molecules. The cDNA encoding one such transacting factor that binds to the cis-acting element known as the Y box has been cloned.