title: Lethal giant larvae-1 deficiency enhances the CD8(+) effector T-cell response to antigen challenge in vivo.
abstract: Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient for Lgl-1. Lgl-1 deficiency did not impair the activation or function of peripheral CD8(+) T cells in response to antigen presentation in vitro, but did skew effector and memory T-cell differentiation. When challenged with antigen-expressing virus or tumor, Lgl-1-deficient mice displayed altered T-cell responses. This manifested in a stronger antiviral and antitumor effector CD8(+) T-cell response, the latter resulting in enhanced control of MC38-OVA tumors. These results reveal a novel role for Lgl-1 in the regulation of virus-specific T-cell responses and antitumor immunity.
authors.affiliation: Cancer Immunology Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Ramsbottom
authors.affiliation: Cancer Immunology Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Faruk
authors.initials: F
authors.lastname: Sacirbegovic
authors.affiliation: Cancer Immunology Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Lo Celso Laboratory, Imperial College London, Sir Alexander Fleming Building, London, UK.
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Hawkins
authors.affiliation: Division of Molecular Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.affiliation: Division of Molecular Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.affiliation: Cancer Immunology Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Van Ham
authors.affiliation: Cancer Immunology Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Haynes
authors.affiliation: Cancer Immunology Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Durrant
authors.affiliation: Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.|Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia.|Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Humbert
authors.affiliation: Cancer Immunology Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.|Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.|Centre for Micro-photonics, Swinburne University of Technology, Hawthorn, Victoria, Australia.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Russell
authors.affiliation: Cancer Immunology Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.|Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Oliaro
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D006023:Glycoproteins / Q000172:deficiency*; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype
chemical_list: D000941:Antigens; D006023:Glycoproteins; C524369:LGL1 protein, mouse