Lectins as pattern recognition molecules: the effects of epitope density in innate immunity.
The innate immune response of multicellular organisms is initiated by the binding of soluble and membrane-bound host molecules including lectins to the surface of pathogenic organisms. Until recently, it was believed that the epitopes recognized by host molecules were uniquely associated with the pathogenic organisms. Hence, the term pattern recognition receptors (PRRs) was used to describe their binding specificities. However, with an expanding number of lectin classes including C-type lectins, siglecs, and galectins recognized as PRRs, it is apparent that many of the glycan epitopes recognized on foreign pathogens are present in the host and involved in cellular functions. Hence, the molecular basis for pattern recognition by lectins of carbohydrate epitopes on pathogens is in question. A number of studies indicate that the density and number of glycan epitopes in multivalent carbohydrates and glycoprotein receptors determine the affinity of lectins and their effector functions. This paper reviews lectins that are involved in innate immunity, mechanisms of enhanced affinity and cross-linking of lectins with density-dependent glycan epitopes, density-dependent recognition of glycan receptors by lectins in host systems and lectin-glycan interactions in foreign pathogens. Evidence indicates that lectin pattern recognition in innate immunity is part of a general mechanism of density-dependent glycan recognition. This leads to a new definition of lectin receptor in biological systems, which considers the density and number of glycan epitopes on the surface of cells and not just the affinity of single epitopes.
Dam
Tarun K
TK
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Brewer
C Fred
CF
D000818:Animals; D001665:Binding Sites; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D037102:Lectins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008954:Models, Biological; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D037102:Lectins; D011134:Polysaccharides