2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is a ligand for CD48

2B4 is a cell surface glycoprotein related to CD2 and implicated in the reg ulation of natural killer and T lymphocyte function. A recombinant protein containing the extracellular region of mouse (m)2B4 attached to avidin-coat ed fluorescent beads bound to rodent cells, and binding was completely bloc ked by CD48 monoclonal antibodies (mAbs). Using surface plasmon resonance, we showed that purified soluble mCD48 bound m2B4 with a six- to ninefold hi gher affinity (K-d approximate to 16 mu M at 37 degrees C) than its other l igand, CD2. Human CD48 bound human 2B4 with a similar affinity (K-d approxi mate to 8 mu M). The finding of an additional ligand for CD48 provides an e xplanation for distinct functional effects observed on perturbing CD2 and C D48 with mAbs or by genetic manipulation.