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

Su Jin Hwang, Amy C. Palin, Li Qi 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

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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.

Original languageEnglish (US)
Article number6982
JournalNature communications
Volume6
DOIs
StatePublished - May 11 2015

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    Hwang, S. J., Palin, A. C., Li, L. Q., Song, K. D., Lee, J., Herz, J., Tubo, N., Chu, H., Pepper, M., Lesourne, R., Zvezdova, E., Pinkhasov, J., Jenkins, M. K., McGavern, D., & Love, P. E. (2015). TCR ITAM multiplicity is required for the generation of follicular helper T-cells. Nature communications, 6, [6982]. https://doi.org/10.1038/ncomms7982