Liu Huanliang, Zhu Tuofu
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Methods Mol Biol. 2005;304:471-81. doi: 10.1385/1-59259-907-9:471.
DC-SIGN and DC-SIGNR efficiently bind HIV-1 and other viral as well as nonviral pathogens and assist either cis or trans infection. Both are type II transmembrane proteins that consist of an N-terminal cytoplasmic domain, a repeat region consisting of seven 23-amino-acid tandem repeats, and a C-terminal C-type carbohydrate recognition domain that binds mannose-enriched carbohydrate modifications of host and pathogen proteins. The normal functions of DC-SIGN and DC-SIGNR include binding to ICAM-2 and ICAM-3. Binding of DC-SIGN to ICAM-2 on endothelial cells facilitates chemokine-induced dendritic cell extravasation; binding to ICAM-3 on T lymphocytes provides the initial step for establishing cell-mediated immunity. Based on the number of tandem repeats, DC-SIGNR is highly polymorphic in the repeat region, while variations in DC-SIGN repeat region are rare. A change in the number of DC-SIGN and DC-SIGNR repeats may influence their normal functions as well as their binding capacity to viral and nonviral pathogens. This chapter describes the methods for detection of DC-SIGN and DC-SIGNR repeat region variations by polymerase chain reaction.
DC-SIGN和DC-SIGNR能有效结合HIV-1及其他病毒和非病毒病原体，并协助顺式或反式感染。二者均为II型跨膜蛋白，由一个N端胞质结构域、一个由七个23个氨基酸的串联重复序列组成的重复区域以及一个C端C型碳水化合物识别结构域组成，该结构域可结合宿主和病原体蛋白中富含甘露糖的碳水化合物修饰。DC-SIGN和DC-SIGNR的正常功能包括与细胞间黏附分子-2（ICAM-2）和细胞间黏附分子-3（ICAM-3）结合。DC-SIGN与内皮细胞上的ICAM-2结合有助于趋化因子诱导的树突状细胞外渗；与T淋巴细胞上的ICAM-3结合是建立细胞介导免疫的第一步。基于串联重复序列的数量，DC-SIGNR在重复区域具有高度多态性，而DC-SIGN重复区域的变异很少见。DC-SIGN和DC-SIGNR重复序列数量的变化可能会影响它们的正常功能以及它们与病毒和非病毒病原体的结合能力。本章介绍了通过聚合酶链反应检测DC-SIGN和DC-SIGNR重复区域变异的方法。
