2B4 stimulation of YT cells induces natural killer cell cytolytic functionand invasiveness

2B4 is a surface molecule found on all human natural killer (NK) cells, a s ubset of CD8(+) T cells, monocytes and basophils. It was originally identif ied on mouse NK cells and the subset of T cells that mediate non-major hist ocompatibility complex (MHC)-restricted killing. Recently,(9) we have clone d the human homologue of 2B4 (h2B4) and found h2B4 to also mediate non-MHC- restricted cytotoxicity. In this study, we examine h2B4 in regulating vario us functions of NK cells using a human NK cell line YT, with monoclonal ant ibody (mAb) C1.7, an antibody that specifically recognizes h2B4. Ligation o f surface 2B4 with mAb C1.7 increases YT's ability to destroy tumour cells. In the presence of mAb C1.7, the production of interferon-gamma (IFN-gamma ) by YT cells is greatly enhanced. Engagement of surface 2B4 by mAb C1.7 do wnregulates the expression of h2B4 at the cell surface as well as the expre ssion of h2B4 mRNA. Also, signalling through h2B4 causes the increased expr ession of matrix metalloproteinase-2, a member of the matrix degrading prot einase family. Thus, in addition to modulating cytolytic function and cytok ine production of NK cells, activation through surface 2B4 may play a role in upregulating the machinery for degradation of extracellular matrices to promote invasion of the tumour by NK cells.