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Scientific paper - Original scientific paper
Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity
PLOS Biology, 18 (2020), 3; e3000648. https://doi.org/10.1371/journal.pbio.3000648
Kavazović, Inga; Han, Hongya; Balzaretti, Giulia; Slinger, Erik; Lemmermann, Niels A. W.; ten Brinke, Anja; Merkler, Doron; Koster, Jan; Bryceson, Yenan T.; de Vries, Niek; Jonjić, Stipan; Klarenbeek, Paul L.; Polić, Bojan; Eldering, Eric; Wensveen, Felix M. More authors...

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Kavazović, I., Han, H., Balzaretti, G., Slinger, E., Lemmermann, N. A. W., ten Brinke, A. ... Wensveen, F. M. (2020). Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity. PLOS Biology, 18. (3). doi: 10.1371/journal.pbio.3000648

Kavazović, Inga, et al. "Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity." PLOS Biology, vol. 18, no. 3, 2020. https://doi.org/10.1371/journal.pbio.3000648

Kavazović, Inga, Hongya Han, Giulia Balzaretti, Erik Slinger, Niels A. W. Lemmermann, Anja ten Brinke, Doron Merkler, et al. "Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity." PLOS Biology 18, no. 3 (2020). https://doi.org/10.1371/journal.pbio.3000648

Kavazović, I., et al. (2020) 'Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity', PLOS Biology, 18(3). doi: 10.1371/journal.pbio.3000648

Kavazović I, Han H, Balzaretti G, Slinger E, Lemmermann NAW, ten Brinke A, and sur.. Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity. PLOS Biology [Internet]. 2020 March 17 [cited 2024 May 06];18(3). doi: 10.1371/journal.pbio.3000648

I. Kavazović, et al., "Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity", PLOS Biology, vol. 18, no. 3, March 2020. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:950480. [Accessed: 06 May 2024]

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Metadata
Title (english)Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity
AuthorInga Kavazović
AuthorHongya Han
AuthorGiulia Balzaretti
AuthorErik Slinger
AuthorNiels A. W. Lemmermann
AuthorAnja ten Brinke
AuthorDoron Merkler
AuthorJan Koster
AuthorYenan T. Bryceson
AuthorNiek de Vries
AuthorStipan Jonjić
AuthorPaul L. Klarenbeek
AuthorBojan Polić
AuthorEric Eldering
AuthorFelix M. Wensveen
Author's institutionUniversity of Rijeka
Faculty of Medicine
(Department of Histology and Embryology)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Abstract (english)
The memory CD8 T-cell pool must select for clones that bind immunodominant epitopes with high affinity to efficiently counter reinfection. At the same time, it must retain a level of clonal diversity to allow recognition of pathogens with mutated epitopes. How the level of diversity within the memory pool is controlled is unclear, especially in the context of a selective drive for antigen affinity. We find that preservation of clones that bind the activating antigen with low affinity depends on expression of the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the prosurvival protein Bcl-2. At higher signal intensity, T-bet is induced which suppresses Bcl-2 and causes a relative survival advantage for cells of low affinity. Clones activated with high-affinity antigen form memory largely independent of Eomes and have a proliferative advantage over clones that bind the same antigen with low affinity. This causes high-affinity clones to prevail in the memory pool, despite their relative survival deficit. Genetic or therapeutic targeting of the Eomes/Bcl-2 axis reduces the clonal diversity of the memory pool, which diminishes its ability to respond to pathogens carrying mutations in immunodominant epitopes. Thus, we demonstrate on a molecular level how sufficient diversity of the memory pool is established in an environment of affinity-based selection.
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review - international
Publication versionPublished version
Journal titlePLOS Biology
Numberingvol. 18, no. 3, e3000648
e-ISSN1545-7885
DOIhttps://doi.org/10.1371/journal.pbio.3000648
URN:NBNurn:nbn:hr:184:950480
Publication2020-03-17
ProjectNumber: IP-2016-06-8027
Title (croatian): Preuređivanje memorije: Manipuliranje T-staničnom memorijom u svrhu unapređenja učinkovitosti cjepiva
Acronym: T-MEMORY
Leader: Felix Wensveen
Jurisdiction: Croatia
Funding stream: IP
ProjectNumber: IP-2016-06-9306
Title (croatian): Imunosni mehanizmi u razvoju upale i metaboličkog sindroma u debljini
Acronym: INFLAMETAB
Leader: Bojan Polić
Jurisdiction: Croatia
Funding stream: IP
ProjectNumber: KK.011.1.01.0006
Title (croatian): Jačanje kapaciteta CerVirVac-a za istraživanja u virusnoj imunologiji i vakcinologiji
Leader: Stipan Jonjić
Jurisdiction: eu
ProjectNumber: N/A
Title (croatian): Centar izvrsnosti za virusnu imunologiju i cjepiva
Title (english): Centre of Excellence for Research in Viral Immunology and the Development of New Vaccines
Acronym: CERVirVac
Leader: Stipan Jonjić
Jurisdiction: Croatia
Funding stream: ZCI
Document URLhttps://dx.plos.org/10.1371/journal.pbio.3000648
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2020-03-23 16:48:12