title: Dendritic Cell Migration and Antigen Presentation Are Coordinated by the Opposing Functions of the Tetraspanins CD82 and CD37.
abstract: This study supports a new concept where the opposing functions of the tetraspanins CD37 and CD82 may coordinate changes in migration and Ag presentation during dendritic cell (DC) activation. We have previously published that CD37 is downregulated upon monocyte-derived DC activation, promotes migration of both skin and bone marrow-derived dendritic cells (BMDCs), and restrains Ag presentation in splenic and BMDCs. In this article, we show that CD82, the closest phylogenetic relative to CD37, appears to have opposing functions. CD82 is upregulated upon activation of BMDCs and monocyte-derived DCs, restrains migration of skin and BMDCs, supports MHC class II maturation, and promotes stable interactions between T cells and splenic DCs or BMDCs. The underlying mechanism involves the rearrangement of the cytoskeleton via a differential activation of small GTPases. Both CD37(-/-) and CD82(-/-) BMDCs lack cellular projections, but where CD37(-/-) BMDCs spread poorly on fibronectin, CD82(-/-) BMDCs are large and spread to a greater extent than wild-type BMDCs. At the molecular level, CD82 is a negative regulator of RhoA, whereas CD37 promotes activation of Rac-1; both tetraspanins negatively regulate Cdc42. Thus, this study identifies a key aspect of DC biology: an unactivated BMDC is CD37(hi)CD82(lo), resulting in a highly motile cell with a limited ability to activate naive T cells. By contrast, a late activated BMDC is CD37(lo)CD82(hi), and thus has modified its migratory, cytoskeletal, and Ag presentation machinery to become a cell superbly adapted to activating naive T cells.
authors.affiliation: Department of Immunology and Pathology, Monash University, Melbourne, Victoria 3004, Australia;
authors.forename: Eleanor L
authors.initials: EL
authors.lastname: Jones
authors.affiliation: Department of Immunology and Pathology, Monash University, Melbourne, Victoria 3004, Australia; Department of Medicine, Centre for Inflammatory Diseases, Monash University, Clayton, Victoria 3168, Australia;
authors.forename: Janet L
authors.initials: JL
authors.lastname: Wee
authors.affiliation: Department of Immunology and Pathology, Monash University, Melbourne, Victoria 3004, Australia;
authors.forename: Maria C
authors.identifier: http://orcid.org/0000-0001-6015-5651
authors.initials: MC
authors.lastname: Demaria
authors.affiliation: Department of Immunology and Pathology, Monash University, Melbourne, Victoria 3004, Australia;
authors.forename: Jessica
authors.initials: J
authors.lastname: Blakeley
authors.affiliation: Department of Immunology and Pathology, Monash University, Melbourne, Victoria 3004, Australia;
authors.forename: Po Ki
authors.initials: PK
authors.lastname: Ho
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Melbourne 3010, Australia;
authors.forename: Javier
authors.initials: J
authors.lastname: Vega-Ramos
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Melbourne 3010, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne 3010, Australia;
authors.forename: Jose A
authors.identifier: http://orcid.org/0000-0001-6771-8891
authors.initials: JA
authors.lastname: Villadangos
authors.affiliation: Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, G525 GA Nijmegen, the Netherlands; and.
authors.forename: Annemiek B
authors.identifier: http://orcid.org/0000-0002-3590-2368
authors.initials: AB
authors.lastname: van Spriel
authors.affiliation: Department of Medicine, Centre for Inflammatory Diseases, Monash University, Clayton, Victoria 3168, Australia;
authors.forename: Michael J
authors.identifier: http://orcid.org/0000-0003-2354-357X
authors.initials: MJ
authors.lastname: Hickey
authors.affiliation: Molecular Immunology, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Günther J
authors.initials: GJ
authors.lastname: Hämmerling
authors.affiliation: Department of Immunology and Pathology, Monash University, Melbourne, Victoria 3004, Australia; mark.wright@monash.edu.
authors.forename: Mark D
authors.identifier: http://orcid.org/0000-0002-2177-5214
authors.initials: MD
authors.lastname: Wright
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002465:Cell Movement; D002469:Cell Separation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D051861:Kangai-1 Protein / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D059470:Tetraspanins / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C504565:Cd37 protein, mouse; C497689:Cd82 antigen, mouse; D051861:Kangai-1 Protein; D059470:Tetraspanins