Synaptic clusters of MHC class II molecules induced on DCs by adhesion molecule-mediated initial T-cell scanning.
Initial adhesive contacts between T lymphocytes and dendritic cells (DCs) facilitate recognition of peptide-MHC complexes by the TCR. In this report, we studied the dynamic behavior of adhesion and Ag receptors on DCs during initial contacts with T-cells. Adhesion molecules LFA-1- and ICAM-1,3-GFP as well as MHC class II-GFP molecules were very rapidly concentrated at the DC contact area. Binding of ICAM-3, and ICAM-1 to a lesser extent, to LFA-1 expressed by mature but not immature DC, induced MHC-II clustering into the immune synapse. Also, ICAM-3 binding to DC induced the activation of the Vav1-Rac1 axis, a regulatory pathway involved in actin cytoskeleton reorganization, which was essential for MHC-II clustering on DCs. Our results support a model in which ICAM-mediated MHC-II clustering on DC constitutes a priming mechanism to enhance antigen presentation to T-cells.
de la Fuente
Hortensia
H
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain.
Mittelbrunn
María
M
Sánchez-Martín
Lorena
L
Vicente-Manzanares
Miguel
M
Lamana
Amalia
A
Pardi
Ruggero
R
Cabañas
Carlos
C
Sánchez-Madrid
Francisco
F
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D016000:Cluster Analysis; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D005802:Genes, MHC Class II; D049452:Green Fluorescent Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008863:Microspheres; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013569:Synapses / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; C483616:ICAM3 protein, human; D010455:Peptides; D051567:Proto-Oncogene Proteins c-vav; D011994:Recombinant Proteins; C496618:VAV1 protein, human; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D004247:DNA; D020830:rac1 GTP-Binding Protein