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TCR ITAM multiplicity is required for the generation of follicular helper T-cells

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  • SuJin Hwang

    (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
    Present address: Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC 20037, USA)

  • Amy C. Palin

    (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)

  • LiQi Li

    (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)

  • Ki-Duk Song

    (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
    Present address: Genomic Informatics Center, Hankyong National University, Anseong 456-749, Korea)

  • Jan Lee

    (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)

  • Jasmin Herz

    (Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health)

  • Noah Tubo

    (Center for Immunology, University of Minnesota Medical School
    Present address: Genzyme, a Sanofi company, 49 New York avenue, Framingham, Massachusetts 01702, USA)

  • Hamlet Chu

    (Center for Immunology, University of Minnesota Medical School
    Present address: Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, California 94720-3200, USA)

  • Marion Pepper

    (Center for Immunology, University of Minnesota Medical School
    Present address: Department of Immunology, University of Washington, 750 Republican Street, Seattle, Washington 98109-8059, USA)

  • Renaud Lesourne

    (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
    Present address: Centre de Physiopathologie de Toulouse Purpan, CHU Purpan, BP 3028 31024, Toulouse, France; INSERM, U1043 Toulouse, France; CNRS, UMR5282 Toulouse, France; Université Toulouse III Paul-Sabatier, 31062 Toulouse, France)

  • Ekaterina Zvezdova

    (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
    Present address: Department of Microbiology and Immunology, Columbia University Medical Center,701 West 168th street, New York, New York 10032, USA)

  • Julia Pinkhasov

    (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
    Present address: Division of Rheumatology, David Geffen School of Medicine at UCLA, 1000 Veteran Avenue, Room 35-40, Los Angeles, California 90024, USA)

  • Marc K. Jenkins

    (Center for Immunology, University of Minnesota Medical School)

  • Dorian McGavern

    (Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health)

  • Paul E. Love

    (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)

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.

Suggested Citation

  • SuJin Hwang & Amy C. Palin & LiQi Li & Ki-Duk Song & Jan Lee & Jasmin Herz & Noah Tubo & Hamlet Chu & Marion Pepper & Renaud Lesourne & Ekaterina Zvezdova & Julia Pinkhasov & Marc K. Jenkins & Dorian , 2015. "TCR ITAM multiplicity is required for the generation of follicular helper T-cells," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7982
    DOI: 10.1038/ncomms7982
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    1. Ivy K Brown & Nathan Dyjack & Mindy M Miller & Harsha Krovi & Cydney Rios & Rachel Woolaver & Laura Harmacek & Ting-Hui Tu & Brian P O’Connor & Thomas Danhorn & Brian Vestal & Laurent Gapin & Clemenci, 2021. "Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire," PLOS Pathogens, Public Library of Science, vol. 17(6), pages 1-34, June.

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