Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin

Natural killer (NK) cells are components of the innate immune system that c an recognize and kill virally infected cells, tumor cells, and allogeneic c ells without prior sensitization. NK cells also elaborate cytokines (e.g., interferon-gamma and tumor necrosis factor-alpha) and chemokines (e.g., mac rophage inflammatory protein-1 alpha) that promote the acquisition of antig en-specific immunity. NK cell differentiation is accompanied by the cell su rface expression of a mucin-like glycoprotein bearing an NK cell-restricted keratan sulfate-related lactosamine carbohydrate, the PENS epitope. Here, we report that PENS is a post-translational modification of P-selectin glyc oprotein ligand-1 (PSGL-1). The PENS epitope creates on PSGL-1 a unique bin ding site for L-selectin, which is independent of PSGL-1 tyrosine sulfation . On the surface of NK cells, the expression of PENS is coordinated with th e disappearance of L-selectin and the up-regulation of Killer cell Ig-like Receptors (KIR). These results indicate that NK cell differentiation is acc ompanied by the acquisition of a unique carbohydrate, PENS, that can serve as part of a combination code to deliver KIR+ NK cells to specific tissues.