C33 antigen and M38 antigen recognized by monoclonal antibodies inhibitory to syncytium formation by human T cell leukemia virus type 1 are both members of the transmembrane 4 superfamily and associate with each other and with CD4 or CD8 in T cells.

C33 Ag and M38 Ag had been identified by mAb inhibitory to HTLV-1-induced syncytium formation. The cDNA encoding C33 Ag had revealed that it belongs to the newly defined transmembrane 4 superfamily (TM4SF). M38 Ag was detected on virtually all human cell lines and fresh leukocytes except for most granulocytes. It was also expressed on a mouse hybrid cell clone containing human chromosome 11q23-pter. Immunoprecipitation and immunoblot analyses identified a monomeric 26-kDa protein. The M38 epitope was dependent on S-S bonding. These characteristics were very similar to those reported for TAPA-1 (the target of antiproliferative antibody-1), which also belongs to TM4SF as C33 Ag. We therefore cloned the cDNA of human TAPA-1 and expressed it in COS cells. M38 indeed reacted with COS cells expressing human TAPA-1. We concluded that M38 Ag was identical to TAPA-1. To further investigate the biologic functions of C33 Ag and M38 Ag (TAPA-1) and their roles in HTLV-1-induced syncytium formation, molecules associated with these Ag were examined in T cells. Immunoprecipitation from surface-iodinated cell lysates revealed that proteins co-precipitated by C33 and M38 were mostly common including each other. Sequential immunoprecipitation-immunoblot experiments confirmed that C33 Ag and M38 Ag (TAPA-1) were associated with each other. The association was further confirmed in BHK cells doubly transfected with human cDNA for C33 Ag and TAPA-1. We extended similar analyses and found that C33 Ag and M38 Ag (TAPA-1) were regularly associated with CD4 or CD8. The association of these Ag on the cell surface was further supported by co-modulation of M38 Ag (TAPA-1), CD4 and CD8 with C33 Ag. This is the first time that a physical association between the members of TM4SF is demonstrated. Furthermore, the regular association of C33 Ag and M38 Ag (TAPA-1) with CD4 or CD8 might indicate that they play a role in expression and/or function of the CD4/CD8 co-receptor complex.