van Kooyk Yvette
Department of Molecular Cell Biology and Immunology VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
Biochem Soc Trans. 2008 Dec;36(Pt 6):1478-81. doi: 10.1042/BST0361478.
DCs (dendritic cells) are specialized in the recognition of pathogens and play a pivotal role in the control of immune responses. DCs are also important for homoeostatic control, recognizing self-antigens and tolerizing the tissue environment. The nature of the antigen recognized tilts the balance towards immunity or tolerance. CLRs (C-type lectin receptors) expressed by DC are involved in the recognition and capture of many glycosylated self-antigens and pathogens. It is now becoming clear that these CLRs may not only serve as antigen receptors allowing internalization and antigen presentation, but also function in the recognition of glycosylated self-antigens, and as adhesion and/or signalling molecules. The expression of C-type lectins is very sensitive to maturation stimuli, leading to down-regulation as DCs mature. CLRs such as DC-SIGN (DC-specific intracellular adhesion molecule-3 grabbing non-integrin) recognizes high-mannose-containing structures and Lewis antigens (Le(x), Le(y), Le(b) and Le(a)), whereas the CLR MGL (macrophage galactose/N-acetylgalactosamine-specific C-type lectin) recognizes GalNAc. Le(x), Le(y) and GalNAc glycan structures are often expressed on tumours. We have demonstrated that glycan modification of antigen can strongly enhance MHC class I responses and the induction of antigen-specific cytotoxic T-lymphocytes, indicating that glycosylated antigen targets C-type lectin to enhance antigen-specific T-cell responses. Moreover, these CLRs induce signalling processes in DCs and specific cytokine responses in combination with TLR (Toll-like receptor) triggering. This implies that specific C-type lectin-targeted antigens can regulate T-cell polarization. Understanding the diversity of C-type lectins being expressed on DCs as well as their carbohydrate-specific recognition profiles should promote understanding of pathogen recognition in many diseases, as well as the regulation of cellular interactions of DCs that are essential in the control of immunity.
树突状细胞（DCs）专门负责识别病原体，在免疫反应的控制中发挥关键作用。DCs对于稳态控制也很重要，它们识别自身抗原并使组织环境产生耐受。所识别抗原的性质会使平衡向免疫或耐受方向倾斜。DCs表达的C型凝集素受体（CLRs）参与许多糖基化自身抗原和病原体的识别与捕获。现在越来越清楚的是，这些CLRs不仅可作为允许内化和抗原呈递的抗原受体，还在糖基化自身抗原的识别中发挥作用，并作为黏附分子和/或信号分子。C型凝集素的表达对成熟刺激非常敏感，随着DCs成熟会导致其下调。诸如DC- SIGN（DC特异性细胞间黏附分子3结合非整合素）等CLRs识别含高甘露糖的结构以及Lewis抗原（Le(x)、Le(y)、Le(b)和Le(a)），而CLR MGL（巨噬细胞半乳糖/N-乙酰半乳糖胺特异性C型凝集素）识别N-乙酰半乳糖胺。Le(x)、Le(y)和N-乙酰半乳糖胺聚糖结构常在肿瘤上表达。我们已经证明，抗原的聚糖修饰可强烈增强MHC I类反应以及抗原特异性细胞毒性T淋巴细胞的诱导，这表明糖基化抗原靶向C型凝集素以增强抗原特异性T细胞反应。此外，这些CLRs与Toll样受体（TLR）触发相结合，可在DCs中诱导信号传导过程以及特定的细胞因子反应。这意味着特定的C型凝集素靶向抗原可调节T细胞极化。了解DCs上表达的C型凝集素的多样性及其碳水化合物特异性识别谱，应有助于理解许多疾病中的病原体识别，以及DCs细胞间相互作用的调节，而这种调节在免疫控制中至关重要。
