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

doi:10.1038/ncomms7982

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

Microbiology

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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 language	English (US)
Article number	6982
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7982
State	Published - May 11 2015

Bibliographical note

Funding Information:
This work was funded by the Intramural Research Program of the Eunice Kennedy Shriver, NICHD (PEL: Project number: 1ZIAHD001803-19).

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

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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.",

author = "Hwang, {Su Jin} and Palin, {Amy C.} and Li, {Li Qi} and Song, {Ki Duk} and Jan Lee and Jasmin Herz and Noah Tubo and Hamlet Chu and Marion Pepper and Renaud Lesourne and Ekaterina Zvezdova and Julia Pinkhasov and Jenkins, {Marc K.} and Dorian McGavern and Love, {Paul E.}",

note = "Funding Information: This work was funded by the Intramural Research Program of the Eunice Kennedy Shriver, NICHD (PEL: Project number: 1ZIAHD001803-19). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

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doi = "10.1038/ncomms7982",

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AU - Hwang, Su Jin

AU - Palin, Amy C.

AU - Li, Li Qi

AU - Song, Ki Duk

AU - Lee, Jan

AU - Herz, Jasmin

AU - Tubo, Noah

AU - Chu, Hamlet

AU - Pepper, Marion

AU - Lesourne, Renaud

AU - Zvezdova, Ekaterina

AU - Pinkhasov, Julia

AU - Jenkins, Marc K.

AU - McGavern, Dorian

AU - Love, Paul E.

N1 - Funding Information: This work was funded by the Intramural Research Program of the Eunice Kennedy Shriver, NICHD (PEL: Project number: 1ZIAHD001803-19). Publisher Copyright: © 2015 Macmillan Publishers Limited.

PY - 2015/5/11

Y1 - 2015/5/11

N2 - 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.

AB - 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.

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

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