The human histocompatibility leukocyte antigen (HLA) class II-associated invariant chain is composed of at least four polypeptides. One of these polypeptide chains is expressed as a membrane-bound subunit and has been designated CD74. The loading of peptide onto the class II MHC protein (MHC II) appears to be regulated by CD74, which associates with MHC II during its migration to the endosomal compartment, where class II binds peptide. CD74 is expressed by cells of both T lymphocyte and B lymphocyte lineages. In fact, CD74 is broadly expressed in normal B lymphocytes, regardless of their histocompatibility leukocyte antigen (HLA) phenotype, while a subset of peripheral T lymphocytes that are MHC II negative do not express CD74.