Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

IL-15 Trans-Presentation Is an Autonomous, Antigen-Independent Process

Ádám Kenesei, Julianna Volkó, Nikoletta Szalóki, Gábor Mocsár, Károly Jambrovics, Zoltán Balajthy, Andrea Bodnár, Katalin Tóth, Thomas A. Waldmann and György Vámosi
J Immunol November 15, 2021, 207 (10) 2489-2500; DOI: https://doi.org/10.4049/jimmunol.2100277
Ádám Kenesei
*Department of Biophysics and Cell Biology, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ádám Kenesei
Julianna Volkó
*Department of Biophysics and Cell Biology, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nikoletta Szalóki
*Department of Biophysics and Cell Biology, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gábor Mocsár
*Department of Biophysics and Cell Biology, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gábor Mocsár
Károly Jambrovics
†Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zoltán Balajthy
†Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Zoltán Balajthy
Andrea Bodnár
*Department of Biophysics and Cell Biology, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katalin Tóth
‡Division of Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas A. Waldmann
§Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
György Vámosi
*Department of Biophysics and Cell Biology, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for György Vámosi
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Key Points

  • IL-15 trans-presentation (TP) and Ag presentation rely on APC–T cell interaction.

  • We showed IL-15R subunit assembly upon TP and joint motion with MHC to the IS.

  • IL-15R and TCR do not amplify each other’s signaling; TP is self-sufficient.

Visual Abstract

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Abstract

IL-15 plays a pivotal role in the long-term survival of T cells and immunological memory. Its receptor consists of three subunits (IL-15Rα, IL-2/15Rβ, and γc). IL-15 functions mainly via trans-presentation (TP), during which an APC expressing IL-15 bound to IL-15Rα presents the ligand to the βγc receptor-heterodimer on a neighboring T/NK cell. To date, no direct biophysical evidence for the intercellular assembly of the IL-15R heterotrimer exists. Ag presentation (AP), the initial step of T cell activation, is also based on APC–T cell interaction. We were compelled to ask whether AP has any effect on IL-15 TP or whether they are independent processes. In our human Raji B cell–Jurkat T cell model system, we monitored inter-/intracellular protein interactions upon formation of IL-15 TP and AP receptor complexes by Förster resonance energy transfer measurements. We detected enrichment of IL-15Rα and IL-2/15Rβ at the synapse and positive Förster resonance energy transfer efficiency if Raji cells were pretreated with IL-15, giving direct biophysical evidence for IL-15 TP. IL-15Rα and MHC class II interacted and translocated jointly to the immunological synapse when either ligand was present, whereas IL-2/15Rβ and CD3 moved independently of each other. IL-15 TP initiated STAT5 phosphorylation in Jurkat cells, which was not further enhanced by AP. Conversely, IL-15 treatment slightly attenuated Ag-induced phosphorylation of the CD3ζ chain. Our studies prove that in our model system, IL-15 TP and AP can occur independently, and although AP enhances IL-15R assembly, it has no significant effect on IL-15 signaling during TP. Thus, IL-15 TP can be considered an autonomous, Ag-independent process.

Footnotes

  • This work was supported by the intramural research program of the National Cancer Institute, National Institutes of Health (to T.A.W.); Grants GINOP-2.3.2-15-2016-00026, NN129371, and ANN135107 from the National Research, Development and Innovation Office, Hungary (to G.V.); Grant EFOP-3.6.3-VEKOP-16-2017-00009 cofinanced by the European Union and the European Social Fund (to A.B.); and the Deutscher Akademischer Austauschdienst and the Tempus Közalapítvány under Grant 273478 (to G.V. and K.T.).

  • Á.K., J.V., G.M., and K.J. performed measurements; Á.K. and N.S. prepared reagents and cell lines; Á.K., G.M., K.T., K.J., Z.B., A.B., and G.V. analyzed data; Á.K., G.V., and T.A.W. drafted the manuscript; all authors edited the manuscript; and G.V. and T.A.W. conceptualized the work.

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article

    AP
    Ag presentation
    DC
    dendritic cell
    EGFP
    enhanced GFP
    FLIM
    fluorescence-lifetime imaging microscopy
    FRET
    Förster resonance energy transfer
    IRF
    instrument response function
    IS
    immunological synapse
    Kv
    voltage-gated potassium
    MHC II
    MHC class II
    mTOR
    mammalian target of rapamycin
    SEE
    Staphylococcus enterotoxin E
    TP
    trans-presentation
    Treg
    regulatory T

  • Received March 22, 2021.
  • Accepted September 10, 2021.
  • Copyright © 2021 by The American Association of Immunologists, Inc.
View Full Text

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.50

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Log in using your username and password

Forgot your user name or password?
PreviousNext
Back to top

In this issue

The Journal of Immunology: 207 (10)
The Journal of Immunology
Vol. 207, Issue 10
15 Nov 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
IL-15 Trans-Presentation Is an Autonomous, Antigen-Independent Process
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
IL-15 Trans-Presentation Is an Autonomous, Antigen-Independent Process
Ádám Kenesei, Julianna Volkó, Nikoletta Szalóki, Gábor Mocsár, Károly Jambrovics, Zoltán Balajthy, Andrea Bodnár, Katalin Tóth, Thomas A. Waldmann, György Vámosi
The Journal of Immunology November 15, 2021, 207 (10) 2489-2500; DOI: 10.4049/jimmunol.2100277

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
IL-15 Trans-Presentation Is an Autonomous, Antigen-Independent Process
Ádám Kenesei, Julianna Volkó, Nikoletta Szalóki, Gábor Mocsár, Károly Jambrovics, Zoltán Balajthy, Andrea Bodnár, Katalin Tóth, Thomas A. Waldmann, György Vámosi
The Journal of Immunology November 15, 2021, 207 (10) 2489-2500; DOI: 10.4049/jimmunol.2100277
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Visual Abstract
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Naturally Occurring Anti-Idiotypic Antibodies Portray a Largely Private Repertoire in Immune-Mediated Thrombotic Thrombocytopenic Purpura
  • Berberine Modulates Macrophage Activation by Inducing Glycolysis
  • Adipocyte CD1d Gene Transfer Induces T Cell Expansion and Adipocyte Inflammation in CD1d Knockout Mice
Show more IMMUNE REGULATION

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • FAR 889
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2022 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606