NKR-P1A PROTEIN, AN ACTIVATING RECEPTOR OF RAT NATURAL-KILLER-CELLS, BINDS TO THE CHITOBIOSE CORE OF INCOMPLETELY GLYCOSYLATED N-LINKED GLYCANS, AND TO LINEAR CHITOOLIGOMERS

NKR-P1 represent a family of activating receptors in rodent natural ki ller cells related to C-type animal lectins. We identify here the elem ents involved in the reactivity of the major receptor of rat, NKR-P1A, with N-linked oligosaccharides of glycoproteins. Plate inhibition ass ays with isolated, structurally defined N-glycans as inhibitors of bin ding of NKR-P1A to GlcNAc(16-) BSA revealed that the removal of both t he external sialic acids and the penultimate galactose residues result ed in attaining of significant inhibitory activities. Surprisingly, ad ditional plate inhibition and glycoprotein overlay experiments brought evidence that the core chitobiose, depending on its substitution, can per se support the interaction with NKR-P1A. In a series of linear ch itooligomers (n = 2-7), the inhibitory activities reached a maximum fo r the chitotetraose. The ability of NKR-P1 to recognize both the perip hery and the core region of complex type oligosaccharides may define i ts dual specificity towards carbohydrate components of eukaryotic (e.g ., tumor) cell surfaces, but also reflect an evolutionarily conserved reactivity with microbial saccharides important in immune recognition and signaling functions. (C) 1997 Academic Press.