System-wide Analysis of the T Cell Response

Ruxandra Covacu; Hagit Philip; Merja Jaronen; Jorge Almeida; Jessica E. Kenison; Samuel Darko; Chun Cheih Chao; Gur Yaari; Yoram Louzoun; Liran Carmel; Daniel C. Douek; Sol Efroni; Francisco J. Quintana

doi:10.1016/j.celrep.2016.02.056

System-wide Analysis of the T Cell Response

Ruxandra Covacu, Hagit Philip, Merja Jaronen, Jorge Almeida, Jessica E. Kenison, Samuel Darko, Chun Cheih Chao, Gur Yaari, Yoram Louzoun, Liran Carmel, Daniel C. Douek, Sol Efroni, Francisco J. Quintana

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

33 Scopus citations

Abstract

The T cell receptor (TCR) controls the cellular adaptive immune response to antigens, but our understanding of TCR repertoire diversity and response to challenge is still incomplete. For example, TCR clones shared by different individuals with minimal alteration to germline gene sequences (public clones) are detectable in all vertebrates, but their significance is unknown. Although small in size, the zebrafish TCR repertoire is controlled by processes similar to those operating in mammals. Thus, we studied the zebrafish TCR repertoire and its response to stimulation with self and foreign antigens. We found that cross-reactive public TCRs dominate the T cell response, endowing a limited TCR repertoire with the ability to cope with diverse antigenic challenges. These features of vertebrate public TCRs might provide a mechanism for the rapid generation of protective T cell immunity, allowing a short temporal window for the development of more specific private T cell responses.

Original language	English
Pages (from-to)	2733-2744
Number of pages	12
Journal	Cell Reports
Volume	14
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2016.02.056
State	Published - 22 Mar 2016

Bibliographical note

Publisher Copyright:
© 2016 The Authors.

Funding

This work was supported by grants AI075285 and AI093903 from the NIH and a Harry Weaver Scholar Award and grant RG4111A1 from the National Multiple Sclerosis Society to F.J.Q. and grant 2011154 from the BSF to F.J.Q. and S.E. F.J.Q. thanks Maria Ethel del Aguila for useful discussions and support. R.C. is supported by a postdoctoral fellowship from the Swedish Research Council. M.J. is supported by a Sigrid Juselius fellowship, The Paulo Foundation, The Finnish Multiple Sclerosis Foundation, Orion-Farmos Research Foundation, and the Saastamoinen Foundation. This work was funded in part through the intramural program of the National Institute of Allergy and Infectious Diseases, NIH.

Funders	Funder number
Finnish Multiple Sclerosis Foundation
Sigrid Juselius
National Institutes of Health	RG4111A1
National Institute of Allergy and Infectious Diseases	R01AI093903
National Multiple Sclerosis Society	2011154
United States-Israel Binational Science Foundation
Vetenskapsrådet
Orionin Tutkimussäätiö
Paulon Säätiö
Saastamoisen säätiö

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AU - Darko, Samuel

AU - Chao, Chun Cheih

AU - Yaari, Gur

AU - Louzoun, Yoram

AU - Carmel, Liran

AU - Douek, Daniel C.

AU - Efroni, Sol

AU - Quintana, Francisco J.

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System-wide Analysis of the T Cell Response

Abstract

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Funding

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