Siglecs and their roles in the immune system

Abstract

The pioneering studies of Alan F. Williams and colleagues in the 1980s 1 laid the foundations for our current under- standing of the roles of the immunoglobulin superfamily (IgSF) molecules as recognition molecules in the immune system. The immunoglobulin domain is a highly versatile fold that can be used to bind an almost infinite array of molecular structures, as illustrated by antibodies and T-cell receptors. The 'immuno globulin-type' (I-type) lectins are a discrete subset of the IgSF that exploit the remarkable structural diversity of glycans in their recog nition functions 2,3 Abstract | Cell surfaces in the immune system are richly equipped with a complex mixture of glycans, which can be recognized by diverse glycan-binding proteins. The Siglecs are a family of sialic-acid-binding immunoglobulin-like lectins that are thought to promote cell-cell interactions and regulate the functions of cells in the innate and adaptive immune systems through glycan recognition. In this Review, we describe recent studies on signalling mechanisms and discuss the potential role of Siglecs in triggering endocytosis and in pathogen recognition. Finally, we discuss the postulated functions of the recently discovered CD33-related Siglecs and consider the factors that seem to be driving their rapid evolution.