Distribution and Function of Macrophage Galactose-type C-type Lectin 2 (MGL2/CD301b) EFFICIENT UPTAKE AND PRESENTATION OF GLYCOSYLATED ANTIGENS BY DENDRITIC CELLS
Distribution and Function of Macrophage Galactose-type C-type Lectin 2 (MGL2/CD301b) EFFICIENT UPTAKE AND PRESENTATION OF GLYCOSYLATED ANTIGENS BY DENDRITIC CELLS
复制标题
DOI：
10.1074/jbc.m110.113613
复制
发表时间：
2010-06-18
影响因子：
4.8
通讯作者：
Irimura, Tatsuro
中科院分区：
文献类型：
--
作者：
Denda-Nagai, Kaori;Aida, Satoshi;Irimura, Tatsuro
树突状细胞（DC）表达细胞表面凝集素，其可能参与糖基化外源物质的识别、摄取和呈递。一种独特的钙型（C型）凝集素，巨噬细胞半乳糖（Gal）型C型凝集素（MGL/CD301）在DC上表达，由于其对Gal和N-乙酰半乳糖胺（GalNAc）的单糖特异性，被认为参与来自改变的自身和病原体的分子的识别。虽然小鼠有两个MGL基因，Mgl1和Mgl2，但它们的独特作用以前没有被探索过。本报告通过检查其分布和其在DC的抗原呈递中的作用来表征MGL2的性质。我们产生了MGL2特异性单克隆抗体，并通过免疫组织化学和流式细胞术在分离的细胞中检测MGL2表达。与该抗体反应的细胞显示为MGL1表达细胞的一部分，主要是常规DC。骨髓来源的DC（BM-DC）对具有α-GalNAc残基的可溶性聚丙烯酰胺聚合物（PAA）（GalNAc-PAA）的内化由MGL2介导，如通过比较Mgll（-/-）和Mgl2（-/-）BM-DC与野生型BM-DC所揭示的。如胸苷摄取和细胞因子产生所示，与链霉亲和素（SAv）缀合的生物素化GalNAc-PAA通过BM-DC比与SAv或单独的SAv缀合的β-N-乙酰葡糖胺-PAA更有效地呈递给SAv致敏的T细胞。这是第一份证明GalNAc残基参与DC的抗原摄取和呈递，导致CD4（+）T细胞活化的报告。
Dendritic cells (DCs) express cell surface lectins that are potentially involved in the recognition, uptake, and presentation of glycosylated foreign substances. A unique calcium-type (C-type) lectin, the macrophage galactose (Gal)-type C-type lectin (MGL/CD301) expressed on DCs, is thought to participate in the recognition of molecules from both altered self and pathogens due to its monosaccharide specificity for Gal and N-acetylgalactosamine (GalNAc). Although mice have two MGL genes, Mgl1 and Mgl2, their distinct roles have not been previously explored. The present report characterizes the properties of MGL2 by examining its distribution and its role in antigen presentation by DCs. We generated an MGL2-specific monoclonal antibody and examined MGL2 expression in tissues by immunohistochemistry and in isolated cells by flow cytometry. The cells reactive with this antibody were shown to be a portion of MGL1-expressing cells, mostly conventional DCs. Internalization of soluble polyacrylamide polymers (PAA) with a-GalNAc residues (GalNAc-PAA) by bone marrow-derived DCs (BM-DCs) was mediated by MGL2, as revealed by a comparison of Mgl1(-/-) and Mgl2(-/-) BM-DCs with wild-type BM-DCs. Biotinylated GalNAc-PAA conjugated to streptavidin (SAv) was more efficiently presented to SAv-primed T cells by BM-DCs than beta-N-acetylglucosamine-PAA conjugated to SAv or SAv alone as shown by thymidine uptake and cytokine production. This is the first report that demonstrates the involvement of GalNAc residues in antigen uptake and presentation by DCs that lead to CD4(+) T cell activation.