Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses.
Contact between dendritic cells (DC) and resting T cells is essential to initiate a primary immune response. Here, we demonstrate that ICAM-3 expressed by resting T cells is important in this first contact with DC. We discovered that instead of the common ICAM-3 receptors LFA-1 and alphaDbeta2, a novel DC-specific C-type lectin, DC-SIGN, binds ICAM-3 with high affinity. DC-SIGN, which is abundantly expressed by DC both in vitro and in vivo, mediates transient adhesion with T cells. Since antibodies against DC-SIGN inhibit DC-induced proliferation of resting T cells, our findings predict that DC-SIGN enables T cell receptor engagement by stabilization of the DC-T cell contact zone.
Geijtenbeek
T B
TB
Department of Tumor Immunology, University Medical Center St. Radboud, Nijmegen, The Netherlands.
Torensma
R
R
van Vliet
S J
SJ
van Duijnhoven
G C
GC
Adema
G J
GJ
van Kooyk
Y
Y
Figdor
C G
CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism; D015703:Antigens, CD; D000943:Antigens, Differentiation; D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D020014:K562 Cells; D037102:Lectins / Q000276:immunology / Q000502:physiology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008351:Mannans / Q000494:pharmacology; D008358:Mannose / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D015728:Receptors, HIV / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014162:Transfection; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D002118:Calcium; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D037102:Lectins; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D008351:Mannans; D008358:Mannose; D011956:Receptors, Cell Surface; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C483616:ICAM3 protein, human