Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells

BY55 is a human cell surface molecule whose expression is restricted to NK cells, a subset of circulating CD8(+) T lymphocytes, and all intestinal int raepithelial T lymphocytes. Here, we report that BY55 is a novel NK recepto r showing broad specificity for both classical and nonclassical MHC class I molecules, and that optimal binding requires a prior aggregation of MHC cl ass I complexes, Using BY55 transfectants, we have identified functional co nsequences of MHC class I/ligand interactions for the class I-bearing cell. The triggering of MHC class I molecules on human T cell clones by BY55 del ivered a potent proliferative signal in the presence of soluble CD3 mAb. Th e costimulatory signal provided by MHC class I ligation was only seen in ac tivated, and not resting, peripheral blood T cells, This observation repres ents an additional and/or alternative pathway to CD28 costimulation and may be of particular relevance in memory T cells lacking CD28, such as intesti nal intra-epithelial T lymphocytes, which are CD28(-) but BY55(+).