The N2B2 antibody reacts with mouse TRAIL (TNF-Related Apoptosis-Inducing Ligand, also known as APO-2 ligand or Ly-81), a 40-kDa type-II transmembrane protein of the TNF family. This antibody recognizes mouse Trail-transfected 2PK-3 cells, but not the parental cell line. TRAIL selectively induces apoptosis in various transformed cells, but not in normal cells. Five receptors have been identified for human TRAIL, whereas only one receptor has been described for the mouse counterpart thus far. The pattern of expression of mouse TRAIL is controversial. TRAIL has been detected, with a rabbit polyclonal antibody, on the surface of activated CD4+ and CD8+ T lymphocytes, as well as on CD45R/B220+ lymphocytes, and transformed T- and B-cell lines. Similar results were obtained by western blot and mRNA analyses. However, these results could not be reproduced with the N2B2 mAb. TRAIL expression, detected with the N2B2 mAb, is induced on CD3- NK1.1+ cells after stimulation with IL-2 or IL-15. However, neither freshly isolated nor activated T cells showed TRAIL expression on the cell surface. Furthermore, TRAIL mediates NK-cell cytotoxicity, which is blocked by the N2B2 mAb. TRAIL has been renamed as CD253 recently.