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, Paul E Love

Index: Nat. Commun. 6 , 6982, (2015)

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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.