Human cytomegalovirus antigen presentation by HLA-G in infected cells

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• dc.contributor.author Altadill, Mireia
• dc.contributor.author Álvarez, Iñaki
• dc.contributor.author Ataya Fernández, Michelle, 1993-
• dc.contributor.author Heredia, Gemma
• dc.contributor.author Alari-Pahissa, Elisenda
• dc.contributor.author Muntasell i Castellví, Aura, 1972-
• dc.contributor.author Llano, Manuel
• dc.contributor.author Fuchs, Jonas
• dc.contributor.author Vilches, Carlos
• dc.contributor.author Hengel, Hartmut
• dc.contributor.author Halenius, Anne
• dc.contributor.author López-Botet, M. (Miguel)
• dc.date.accessioned 2025-06-10T06:13:55Z
• dc.date.available 2025-06-10T06:13:55Z
• dc.date.issued 2025
• dc.description.abstract HLA-E and -G class Ib molecules were considered unrelated to viral antigen presentation. HLA-E binds nonamers from the leader sequences of other HLA-I molecules and the human cytomegalovirus (HCMV) UL40 protein, interacting with CD94/NKG2 NK cell receptors. Yet, evidence that HLA-E may present some pathogen-derived peptides to CD8+ T lymphocytes has been reported. By contrast, HLA-G binds a broad spectrum of endogenous sequences but its role in antigen presentation is unknown. An experimental approach was set up to search for HCMV antigens displayed by HLA-G in infected cells. Among the analysed peptidome, 22 sequences corresponding to 16 HCMV molecules were identified; 17 peptides were confirmed to interact in vitro with HLA-G of which 10 displayed characteristic anchor residues. As compared to the response in short-term (6 h) assays to immunodominant IE-1 and pp65 antigens, none of the HLA-G-binding peptides stimulated cytokine production by CD8+ T cells from HCMV-seropositive blood donors (n = 15). Following a 14-day peptide stimulation of PBMC and expansion with IL-2, CD8+ T cells specifically responding to a subset of these viral antigens were detected in some individuals, yet were not restricted by HLA-G in functional assays. A subset of viral peptides did bind to both HLA-G and -E but were not recognised by CD94/NKG2 NK cell receptors. Our results provide the first evidence that HLA-G may display potentially immunogenic viral peptides in HCMV-infected cells, yet do not support their ability to promote HLA-G-restricted CD8+ T cell responses nor to modulate NK cell functions.
• dc.description.sponsorship The work was supported by the Agencia Estatal de Investigación-FEDER (PID2019-110609RB-C21-C22/AEI/10.13039/501100011033) and the Deutsche Forschungsgemeinschaft: grant FOR2830, project HA 6035/2-2 (A.H.) and HE 2526/9-2 (H.H.).
• dc.format.mimetype application/pdf
• dc.identifier.citation Altadill M, Álvarez I, Ataya M, Heredia G, Alari-Pahissa E, Muntasell A, et al. Human cytomegalovirus antigen presentation by HLA-G in infected cells. HLA. 2025 May;105(5):e70089. DOI: 10.1111/tan.70089
• dc.identifier.doi http://dx.doi.org/10.1111/tan.70089
• dc.identifier.issn 2059-2302
• dc.identifier.uri http://hdl.handle.net/10230/70643
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof HLA. 2025 May;105(5):e70089
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C21
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22
• dc.rights © 2025 The Author(s). HLA: Immune Response Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword HLA‐E
• dc.subject.keyword HLA‐G
• dc.subject.keyword NK cell
• dc.subject.keyword T lymphocyte
• dc.subject.keyword Cytomegalovirus
• dc.title Human cytomegalovirus antigen presentation by HLA-G in infected cells
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion