Cutting edge: dendritic cell actin cytoskeletal polarization during immunological synapse formation is highly antigen-dependent.
Dendritic cells (DC) actively rearrange their actin cytoskeleton to participate in formation of the immunological synapse (IS). In this study, we evaluated the requirements for DC participation in the IS. DC rearrange their actin cytoskeleton toward naive CD4(+) T cells only in the presence of specific MHC-peptide complexes. In contrast, naive CD4(+) T cells polarized their cytoskeletal proteins in the absence of Ag. DC cytoskeletal rearrangement occurred at the same threshold of peptide-MHC complexes as that required for T cell activation. Furthermore, T cell activation was inhibited by specific blockade of DC cytoskeletal rearrangement. When TCR-MHC interaction was bypassed by using Con A-activated T cells, DC polarization was abrogated. In addition, directional ligation of MHC class II resulted in DC cytoskeletal polarization. Our findings suggest that a high Ag specificity is required for DC IS formation and that MHC class II signaling plays a central role in this process.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Monther M
MM
Al-Alwan
Robert S
RS
Liwski
S M Mansour
SM
Haeryfar
William H
WH
Baldridge
David W
DW
Hoskin
Geoffrey
G
Rowden
Kenneth A
KA
West
D000199:Actins / Q000378:metabolism* / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000502:physiology*; D002449:Cell Aggregation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000276:immunology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000199:Actins; D000941:Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010455:Peptides