A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions

Summary: Dendritic cells (DC) are present in essentially every tissue, where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen‐derived peptides to T cells. Cell–cell interactions between DC, T cells and endothelial cells are crucial to all immunological processes. Recently, several C‐type lectin receptors have been characterized that are abundantly expressed on the surface of DC. It is now becoming clear that these lectin receptors serve not only as antigen‐receptors recognizing pathogens, but they may also function as adhesion receptors and/or signaling molecules. In particular the DC specific C‐type lectin DC‐SIGN (CD209) regulates adhesion processes, such as DC trafficking by interacting with ICAM‐2 and T cell synapse formation, upon binding of ICAM‐3. C‐type lectins such as DC‐SIGN contain a lectin domain that recognizes in a Ca 2+ ‐dependent manner carbohydrates such as mannose‐containing structures presented on the glycoproteins ICAM‐2 and ICAM‐3. Although the integrin LFA‐1 is a counter‐receptor for both ICAM‐2 and ICAM‐3, on DC, DC‐SIGN is the high affinity adhesion receptor for ICAM‐2/‐3. Here we discuss how the heterogeneity of mannose‐residues exposed on cellular proteins and pathogens regulates specific binding of a repertoire of DC‐expressed C‐type lectins that contribute to the diversity of immune responses created by DC.