Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Netherlands ; Centre for Specialized Nutrition, Danone Research Wageningen, Netherlands.
Front Immunol. 2013 May 6;4:103. doi: 10.3389/fimmu.2013.00103. eCollection 2013.
The zwitterionic capsular polysaccharide A (PSA) of Bacteroides fragilis is the first carbohydrate antigen described to be presented in major histocompatibility complex (MHC) class II for the induction of CD4(+) T cell responses. However, the identity of the receptor mediating binding and internalization of PSA in antigen presenting cells remains elusive. C-type lectins are glycan-binding receptors known for their capacity to target ligands for antigen presentation to T cells. Here, we investigated whether C-type lectins were involved in the internalization of PSA and identified dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) as the main receptor for PSA on human dendritic cells (DC). The induction of PSA-specific T cell proliferation appeared to be completely dependent on DC-SIGN. These data reveal a crucial role for DC-SIGN in the endocytosis and routing of PSA in human DC for the efficient stimulation of PSA-specific CD4(+) T cells.
脆弱拟杆菌的两性离子荚膜多糖 A (PSA) 是第一个被描述为在主要组织相容性复合体 (MHC) Ⅱ类中呈现的碳水化合物抗原,可诱导 CD4(+) T 细胞应答。然而,介导 PSA 在抗原呈递细胞中结合和内化的受体仍不清楚。C 型凝集素是糖结合受体,以其将配体靶向 T 细胞进行抗原呈递的能力而闻名。在这里,我们研究了 C 型凝集素是否参与 PSA 的内化,并鉴定出树突状细胞特异性细胞间黏附分子 3 抓取非整联蛋白 (DC-SIGN) 是人类树突状细胞 (DC) 上 PSA 的主要受体。PSA 特异性 T 细胞增殖的诱导似乎完全依赖于 DC-SIGN。这些数据揭示了 DC-SIGN 在 PSA 内化和人类 DC 中路由中的关键作用,对于有效刺激 PSA 特异性 CD4(+) T 细胞至关重要。