Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Glycobiology. 2010 Mar;20(3):270-9. doi: 10.1093/glycob/cwp186. Epub 2009 Nov 24.
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.
多细胞生物的先天免疫反应是由可溶性和膜结合的宿主分子(包括凝集素)与病原生物体表面的结合引发的。直到最近,人们还认为宿主分子识别的表位与病原生物体独特相关。因此,术语模式识别受体(PRR)被用来描述它们的结合特异性。然而,随着越来越多的凝集素类(包括 C 型凝集素、siglecs 和半乳糖凝集素)被认为是 PRR,许多在外国病原体上识别的糖基表位都存在于宿主中,并参与细胞功能。因此,凝集素识别病原体碳水化合物表位的模式识别的分子基础受到质疑。许多研究表明,多价碳水化合物和糖蛋白受体中糖基表位的密度和数量决定了凝集素的亲和力及其效应功能。本文综述了参与先天免疫的凝集素、凝集素与糖基密度依赖性表位增强亲和力和交联的机制、宿主系统中凝集素对糖受体的密度依赖性识别以及外来病原体中的凝集素-糖相互作用。有证据表明,先天免疫中的凝集素模式识别是糖识别的密度依赖性一般机制的一部分。这导致了生物系统中凝集素受体的新定义,它考虑了细胞表面糖基表位的密度和数量,而不仅仅是单个表位的亲和力。