A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions.
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 Ca2+-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.
van Kooyk
Yvette
Y
Department of Molecular Cell Biology, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands. Y.van_Kooyk.cell@med.vu.nl
Geijtenbeek
Teunis B H
TB
D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin