Carbohydrate-mediated recognition systems in innate immunity

There is growing interest in carbohydrate recognizing receptors of the inna te immune system. Among them are members of the C-type lectin family, which include the collectins and the selectins and which operate by ligating exo genous (microbial) or endogenous carbohydrates. De novo assignments of the sequences of ligands for carbohydrate-recognizing receptors are among the m ost challenging topics in cell biology. This is because of the heterogeneit y of oligosaccharides on proteins and lipids, and their availability only i n limited amounts. To address the need for a microprocedure for direct bind ing studies with oligosaccharides derived from glycoproteins, we introduced the neoglycolipid technology for generating solid phase oligosaccharide pr obes for binding experiments. The technology has enabled assignments of uns uspected oligosaccharide ligands for the selectins and given valuable insig hts into those for the collectins. The ligands so far identified appear not to be unique for a given receptor system; there are considerable cross-rea ctions. Specificity can be created, however, through different modes of oli gosaccharide presentation on macromolecular carriers, or the expression of a particular oligosaccharide sequence on a selected cell type in a given bo dy compartment, and the regulated expression of the receptor protein at the desired location. The existence of unique ligand structures is not ruled o ut, however. Coligation of a receptor may also occur to a second carbohydra te or even to a non-carbohydrate ligand to create a unique assembly. A furt her group of C-type lectin-like proteins occurs on natural killer (NK) cell s and NK T cells, and is associated with activation or inhibition of the ce ll effector functions. An important challenge is to determine whether carbo hydrates are among physiological ligands for this important group of recept ors.