title: Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.
abstract: Voltage-gated Kv1.3 and Ca2+-dependent KCa3.1 are the most prevalent K+channels expressed by human and rat T cells. Despite the preferential upregulation of Kv1.3 over KCa3.1 on autoantigen-experienced effector memory T cells, whether Kv1.3 is required for their induction and function is unclear. Here we show, using Kv1.3-deficient rats, that Kv1.3 is involved in the development of chronically activated antigen-specific T cells. Several immune responses are normal in Kv1.3 knockout (KO) rats, suggesting that KCa3.1 can compensate for the absence of Kv1.3 under these specific settings. However, experiments with Kv1.3 KO rats and Kv1.3 siRNA knockdown or channel-specific inhibition of human T cells show that maximal T-cell responses against autoantigen or repeated tetanus toxoid stimulations require both Kv1.3 and KCa3.1. Finally, our data also suggest that T-cell dependency on Kv1.3 or KCa3.1 might be irreversibly modulated by antigen exposure.
authors.affiliation: Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Chiang
authors.affiliation: Department of Biochemical and Cellular Pharmacology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Tianbo
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Translational Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Surinder
authors.initials: S
authors.lastname: Jeet
authors.affiliation: Department of Translational Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Peng
authors.affiliation: Department of Translational Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Translational Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.affiliation: Department of Translational Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: DeVoss
authors.affiliation: Department of Pathology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Patrick
authors.identifier: 0000-0002-3411-1257
authors.initials: P
authors.lastname: Caplazi
authors.affiliation: Department of Biochemical and Cellular Pharmacology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Søren
authors.initials: S
authors.lastname: Warming
authors.affiliation: Department of Neurobiology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Hackos
authors.affiliation: Department of Structural Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Susmith
authors.initials: S
authors.lastname: Mukund
authors.affiliation: Department of Structural Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Koth
authors.affiliation: Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Grogan
mesh_terms: D000818:Animals; D000939:Epitopes / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007156:Immunologic Memory / Q000187:drug effects; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency / Q000378:metabolism*; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D010641:Phenotype; D026902:Potassium Channel Blockers / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000939:Epitopes; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; C491575:Kcnn4 protein, rat; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D034741:RNA, Small Interfering