The 4F9 antigen is a member of the tetra spans transmembrane protein family and functions as an accessory molecule in T cell activation and adhesion.

In this report, we describe a 43- to 50-kDa protein, which may function as a costimulatory molecule for full activation of human T cells. This Ag, defined by a mouse monoclonal antibody (mAb) anti-4F9, is primarily distributed on "helper/inducer" or "memory" CD4+CD45RO+ subset. Like mAbs against many other accessory/costimulatory molecules, coimmobilization of anti-4F9 with anti-CD3 resulted in synergistic T cell proliferation. In addition, immobilized anti-4F9 on plastic plates induced T cell spreading characterized by the development of prominent dendritic processes. A cDNA encoding the 4F9 Ag was isolated from a cDNA library constructed from PHA/PMA-activated T cells using a COS cell expression system. The sequence of the cDNA and a homology search revealed that the 4F9 Ag was identical to R2, a molecule recently cloned by subtractive hybridization. The 4F9/R2 Ag belongs to a newly identified supergene family (tetra spans transmembrane protein family) characterized by four putative transmembrane domains which are highly conserved between the members of this family. Based upon the phenotypical and functional studies described here, we propose that the 4F9 Ag is an integral membrane protein which can transmit signals involved in T cell proliferation and adhesion. The preferential distribution of this molecule on the CD4+CD45RO+ subset of T cells may contribute to the distinct activation profile and functional repertoire of these cells.