{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:52:10Z","timestamp":1780606330080,"version":"3.54.1"},"reference-count":89,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,17]],"date-time":"2024-03-17T00:00:00Z","timestamp":1710633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-75-00135"],"award-info":[{"award-number":["22-75-00135"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>NK cells play a decisive role in controlling hCMV infection by combining innate and adaptive-like immune reactions. The hCMV-derived VMAPRTLFL (LFL) peptide is a potent activator of NKG2C+ NK cells. Proposed here is an autologous system of LFL stimulation without T lymphocytes and exogenous cytokines that allows us to evaluate NK-cell hCMV-specific responses in more native settings. In this model, we evaluated LFL-induced IFN\u03b3 production, focusing on signaling pathways and the degranulation and proliferation of NK cells orchestrated by microenvironment cytokine production and analyzed the transcriptome of expanded NK cells. NK cells of individuals having high anti-hCMV-IgG levels, in contrast to NK cells of hCMV-seronegative and low-positive donors, displayed increased IFN\u03b3 production and degranulation and activation levels and enhanced proliferation upon LFL stimulation. Cytokine profiles of these LFL-stimulated cultures demonstrated a proinflammatory shift. LFL-induced NK-cell IFN\u03b3 production was dependent on the PI3K and Ras\/Raf\/Mek signaling pathways, independently of cytokines. In hCMV-seropositive individuals, this model allowed obtaining NK-cell antigen-specific populations proliferating in response to LFL. The transcriptomic profile of these expanded NK cells showed increased adaptive gene expression and metabolic activation. The results complement the existing knowledge about hCMV-specific NK-cell response. This model may be further exploited for the identification and characterization of antigen-specific NK cells.<\/jats:p>","DOI":"10.3390\/cells13060530","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T06:58:39Z","timestamp":1710745119000},"page":"530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Autologous T-Cell-Free Antigen Presentation System Unveils hCMV-Specific NK Cell Response"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3378-6508","authenticated-orcid":false,"given":"Maria O.","family":"Ustiuzhanina","sequence":"first","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5403-0753","authenticated-orcid":false,"given":"Maria A.","family":"Streltsova","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita D.","family":"Timofeev","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim A.","family":"Kryukov","sequence":"additional","affiliation":[{"name":"Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy M.","family":"Chudakov","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"},{"name":"Institute of Translational Medicine, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"},{"name":"Central European Institute of Technology, Masaryk University, 60200 Brno, Czech Republic"},{"name":"Abu Dhabi Stem Cells Center, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Kovalenko","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41423-019-0206-4","article-title":"Human NK Cells: Surface Receptors, Inhibitory Checkpoints, and Translational Applications","volume":"16","author":"Sivori","year":"2019","journal-title":"Cell. 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