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

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 McGavern and Paul E. Love ()
Additional contact information
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
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
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
Hamlet Chu: Center for Immunology, University of Minnesota Medical School
Marion Pepper: Center for Immunology, University of Minnesota Medical School
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
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
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
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

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7982

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DOI: 10.1038/ncomms7982

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