Antibodies against a pan-B cell-surface marker have been statistically clustered to define the CDw78 antigen. Molecular characterization of the CDw78 antigen was performed to determine its functional role in T and B cell interactions. Screening a direct expression cDNA library, made from the Epstein-Barr virus-transformed, B lymphoblastoid cell line MP-1 with an anti-CDw78 mAb, we have isolated a 3.8 kb cDNA encoding the transcription factor CIITA, previously shown to transactivate human MHC class II expression. Using several anti-CD78 mAb, we observed induced expression of the CDw78 antigen on the surface of monkey CV-1/EBNA cells transfected with the CIITA cDNA clone. Apparently, recombinant human CIITA can regulate the expression of monkey MHC class II which is recognized by anti-human CDw78 mAb. The anti-human CDw78 mAb seem to recognize a monomorphic determinant of MHC class II. Expression of recombinant human MHC class II antigens in CV-1/EBNA cells was recognized by a panel of CDw78 mAb, as well as by anti-human MHC class II mAb. These data show that the CDw78 antigen is expressed as part of the MHC class II molecule and appears similar if not identical to the alpha beta heterodimeric MHC class II antigen.