C-type lectins on dendritic cells: key modulators for the induction of immune responses

Abstract

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.