The T cell activation molecule H4 and the CD28-like molecule ICOS are identical

The recently cloned CD28-like molecule ICOS displays striking similarities with H4, characterized some years ago in the mouse and recently in humans. Both molecules are selectively expressed by activated and germinal center T cells, display similar structure, and display costimulatory activities. H4 displays lateral association with the CD3/TCR and is expressed by mature t hymocytes. In the mouse, H4 is also expressed at high levels by thymic NKT cells that are resistant to negative selection. The aim of this work was to evaluate whether H4 and ICOS are the same molecule using the C398.4A (bind ing human and mouse H4) and F44 (binding human ICOS) monoclonal antibody (m Ab) in parallel experiments on human T cells. ICOS and H4 displayed the sam e expression pattern in a panel of T cell lines and the same expression kin etics in phytohemagglutinin-activated T cells. C398.4A completely blocked c ell staining by F44, whereas F44 partially blocked C398.4A. H4 and ICOS imm unoprecipitates displayed identical SDS-PAGE patterns and H4 immunoprecipit ation completely removed ICOS from cell lysates. Finally, the C398.4A mAb s pecifically stained cells transfected with the human or mouse ICOS. These d ata prove that H4 and ICOS are the same molecule and that F44 and C398.4A b ind partially different epitopes.