title: TCR ITAM multiplicity is required for the generation of follicular helper T-cells.
abstract: The T-cell antigen receptor (TCR) complex contains 10 copies of a di-tyrosine Immunoreceptor-Tyrosine-based-Activation-Motif (ITAM) that initiates TCR signalling by recruiting protein tyrosine kinases. ITAM multiplicity amplifies TCR signals, but the importance of this capability for T-cell responses remains undefined. Most TCR ITAMs (6 of 10) are contributed by the CD3ζ subunits. We generated 'knock-in' mice that express non-signalling CD3ζ chains in lieu of wild-type CD3ζ. Here we demonstrate that ITAM multiplicity is important for the development of innate-like T-cells and follicular helper T-cells, events that are known to require strong/sustained TCR-ligand interactions, but is not essential for 'general' T-cell responses including proliferation and cytokine production or for the generation of a diverse antigen-reactive TCR repertoire.
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: SuJin
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: Amy C
authors.identifier: 0000000277249563
authors.initials: AC
authors.lastname: Palin
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: LiQi
authors.initials: L
authors.lastname: Li
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: Ki-Duk
authors.identifier: 0000000328270873
authors.initials: KD
authors.lastname: Song
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Lee
authors.affiliation: Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Herz
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Tubo
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Hamlet
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Marion
authors.initials: M
authors.lastname: Pepper
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: Renaud
authors.initials: R
authors.lastname: Lesourne
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Zvezdova
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Pinkhasov
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Marc K
authors.identifier: 0000000180097655
authors.initials: MK
authors.lastname: Jenkins
authors.affiliation: Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Dorian
authors.initials: D
authors.lastname: McGavern
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Love
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D049109:Cell Proliferation; D002999:Clone Cells; D005260:Female; D007156:Immunologic Memory; D061625:Immunoreceptor Tyrosine-Based Activation Motif; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*
chemical_list: D000941:Antigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta