{"doi":"10.4049/jimmunol.2100277","title":"IL-15 <i>Trans</i>-Presentation Is an Autonomous, Antigen-Independent Process","abstract":"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.","journal":"The Journal of Immunology","year":2021,"id":193356,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":761718,"name":"Julianna Volkó","orcid":"0000-0002-6623-012X","position":1,"is_corresponding":false},{"id":762490,"name":"Nikoletta Szalóki","orcid":null,"position":2,"is_corresponding":false},{"id":761719,"name":"Gábor Mocsár","orcid":"0000-0003-0570-3269","position":3,"is_corresponding":false},{"id":762491,"name":"Károly Jambrovics","orcid":null,"position":4,"is_corresponding":false},{"id":761720,"name":"Zoltán Balajthy","orcid":"0000-0001-6654-7234","position":5,"is_corresponding":false},{"id":761721,"name":"Andrea Bodnár","orcid":"0000-0002-9610-4589","position":6,"is_corresponding":false},{"id":561330,"name":"Katalin Tóth","orcid":null,"position":7,"is_corresponding":false},{"id":238492,"name":"Thomas A. Waldmann","orcid":"0000-0003-4500-6660","position":8,"is_corresponding":false},{"id":761722,"name":"György Vámosi","orcid":"0000-0002-7940-2787","position":9,"is_corresponding":false},{"id":761717,"name":"Ádám Kenesei","orcid":"0000-0002-3950-7007","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:49:51.300073Z","pmid":"34654688","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}