title: Actin-bundling protein L-plastin regulates T cell activation.
abstract: Engagement of TCRs induces actin rearrangements, which are critical for T cell activation. T cell responses require new actin polymerization, but the significance of higher-order actin structures, such as microfilament bundles, is unknown. To determine the role of the actin-bundling protein leukocyte-plastin (L-plastin; LPL) in this process, T cells from LPL(-/-) mice were studied. LPL(-/-) T cells were markedly defective in TCR-mediated cytokine production and proliferation. LPL(-/-) T cells also spread inefficiently on surfaces with immobilized TCR ligands and formed smaller immunological synapses with APCs, likely due to defective formation of lamellipodia. LPL(-/-) mice showed delayed rejection of skin allografts after release from immunosuppression. Moreover, LPL(-/-) mice developed much less severe neurologic symptoms in experimental autoimmune encephalomyelitis, which correlated with impaired T cell responses to Ag, manifested by reduced proliferation and production of IFN-γ and IL-17. Thus, LPL-dependent actin bundling facilitates the formation of lamellipodia and normal immunological synapses and thereby enables T cell activation.
authors.affiliation: Department of Microbial Pathogenesis, Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Sharon Celeste
authors.initials: SC
authors.lastname: Morley
authors.forename: David
authors.initials: D
authors.lastname: Donermeyer
authors.forename: Ivan
authors.initials: I
authors.lastname: Peng
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.forename: Jason
authors.initials: J
authors.lastname: Devoss
authors.forename: Dimitry M
authors.initials: DM
authors.lastname: Danilenko
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Lin
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brown
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054992:Immunological Synapses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D000199:Actins; D000941:Antigens; D003598:Cytoskeletal Proteins; D020381:Interleukin-17; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; C066559:Lcp1 protein, mouse; D007371:Interferon-gamma