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001-es BibID:	BIBFORM097487
Első szerző:	Kenesei Ádám
Cím:	IL-15 Trans-Presentation Is an Autonomous, Antigen-Independent Process / Kenesei Ádám, Volkó Julianna, Szalóki Nikoletta, Mocsár Gábor, Jambrovics Károly, Balajthy Zoltán, Bodnár Andrea, Tóth Katalin, Waldmann Thomas A., Vámosi György
Dátum:	2021
ISSN:	0022-1767 1550-6606
Megjegyzések:	IL-15 plays a pivotal role in the long-term survival of T cells and immunological memory. Its receptor consists of three subunits (IL-15R?, IL-2/15R?, and ?c). IL-15 functions mainly via trans-presentation (TP), during which an APC expressing IL-15 bound to IL-15R? presents the ligand to the ??c 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-15R? and IL-2/15R? 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-15R? and MHC class II interacted and translocated jointly to the immunological synapse when either ligand was present, whereas IL-2/15R? 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 CD3? 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.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk interleukin trans-presentation immunology
Megjelenés:	Journal Of Immunology. - 207 : 10 (2021), p. 2489-2500. -
További szerzők:	Volkó Julianna (1983-) (biotechnológus) Szalóki Nikoletta (1981-) (biológus) Mocsár Gábor (1981-) (biofizikus) Jambrovics Károly (1988-) (biológus, gyógyszer-biotechnológus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Dóczy-Bodnár Andrea (1970-) (biofizikus) Tóth Katalin Ágnes (1977-) (biokémikus, molekuláris biológus) Waldmann, Thomas A. Vámosi György (1967-) (biofizikus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00026 GINOP EFOP-3.6.3-VEKOP-16-2017-00009 EFOP Tempus Public Foundation 273478 Egyéb Deutscher Akademischer Austauschdienst 273478 Egyéb HHS \| NIH \| National Cancer Institute intramural research program Egyéb
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