PT  - JOURNAL ARTICLE
AU  - Kenesei, Ádám
AU  - Volkó, Julianna
AU  - Szalóki, Nikoletta
AU  - Mocsár, Gábor
AU  - Jambrovics, Károly
AU  - Balajthy, Zoltán
AU  - Bodnár, Andrea
AU  - Tóth, Katalin
AU  - Waldmann, Thomas A.
AU  - Vámosi, György
TI  - IL-15 <em>Trans</em>-Presentation Is an Autonomous, Antigen-Independent Process
AID  - 10.4049/jimmunol.2100277
DP  - 2021 Nov 15
TA  - The Journal of Immunology
PG  - 2489--2500
VI  - 207
IP  - 10
4099  - http://www.jimmunol.org/content/207/10/2489.short
4100  - http://www.jimmunol.org/content/207/10/2489.full
SO  - J. Immunol.2021 Nov 15; 207
AB  - 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.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.