Human cytomegalovirus antigen presentation by HLA-G in infected cells
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...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/70643 |
| Acceso en línea: | http://hdl.handle.net/10230/70643 http://dx.doi.org/10.1111/tan.70089 |
| Access Level: | acceso abierto |
| Palabra clave: | HLA‐E HLA‐G NK cell T lymphocyte Cytomegalovirus |
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Human cytomegalovirus antigen presentation by HLA-G in infected cellsAltadill, MireiaÁlvarez, IñakiAtaya Fernández, Michelle, 1993-Heredia, GemmaAlari-Pahissa, ElisendaMuntasell i Castellví, Aura, 1972-Llano, ManuelFuchs, JonasVilches, CarlosHengel, HartmutHalenius, AnneLópez-Botet, M. (Miguel)HLA‐EHLA‐GNK cellT lymphocyteCytomegalovirusHLA-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.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.).Wiley202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/70643http://dx.doi.org/10.1111/tan.70089http://hdl.handle.net/10230/70643reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésHLA. 2025 May;105(5):e70089info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C21info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22© 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.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/706432026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Human cytomegalovirus antigen presentation by HLA-G in infected cells |
| title |
Human cytomegalovirus antigen presentation by HLA-G in infected cells |
| spellingShingle |
Human cytomegalovirus antigen presentation by HLA-G in infected cells Altadill, Mireia HLA‐E HLA‐G NK cell T lymphocyte Cytomegalovirus |
| title_short |
Human cytomegalovirus antigen presentation by HLA-G in infected cells |
| title_full |
Human cytomegalovirus antigen presentation by HLA-G in infected cells |
| title_fullStr |
Human cytomegalovirus antigen presentation by HLA-G in infected cells |
| title_full_unstemmed |
Human cytomegalovirus antigen presentation by HLA-G in infected cells |
| title_sort |
Human cytomegalovirus antigen presentation by HLA-G in infected cells |
| dc.creator.none.fl_str_mv |
Altadill, Mireia Álvarez, Iñaki Ataya Fernández, Michelle, 1993- Heredia, Gemma Alari-Pahissa, Elisenda Muntasell i Castellví, Aura, 1972- Llano, Manuel Fuchs, Jonas Vilches, Carlos Hengel, Hartmut Halenius, Anne López-Botet, M. (Miguel) |
| author |
Altadill, Mireia |
| author_facet |
Altadill, Mireia Álvarez, Iñaki Ataya Fernández, Michelle, 1993- Heredia, Gemma Alari-Pahissa, Elisenda Muntasell i Castellví, Aura, 1972- Llano, Manuel Fuchs, Jonas Vilches, Carlos Hengel, Hartmut Halenius, Anne López-Botet, M. (Miguel) |
| author_role |
author |
| author2 |
Álvarez, Iñaki Ataya Fernández, Michelle, 1993- Heredia, Gemma Alari-Pahissa, Elisenda Muntasell i Castellví, Aura, 1972- Llano, Manuel Fuchs, Jonas Vilches, Carlos Hengel, Hartmut Halenius, Anne López-Botet, M. (Miguel) |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
HLA‐E HLA‐G NK cell T lymphocyte Cytomegalovirus |
| topic |
HLA‐E HLA‐G NK cell T lymphocyte Cytomegalovirus |
| description |
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. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/70643 http://dx.doi.org/10.1111/tan.70089 http://hdl.handle.net/10230/70643 |
| url |
http://hdl.handle.net/10230/70643 http://dx.doi.org/10.1111/tan.70089 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
HLA. 2025 May;105(5):e70089 info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C21 info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22 |
| dc.rights.none.fl_str_mv |
http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
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Wiley |
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reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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