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HLA\u2010E binds nonamers from the leader sequences of other HLA\u2010I molecules and the human cytomegalovirus (HCMV) UL40 protein, interacting with CD94\/NKG2 NK cell receptors. Yet, evidence that HLA\u2010E may present some pathogen\u2010derived peptides to CD8+ T lymphocytes has been reported. By contrast, HLA\u2010G 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\u2010G in infected cells. Among the analysed peptidome, 22 sequences corresponding to 16 HCMV molecules were identified; 17 peptides were confirmed to interact in\u00a0vitro with HLA\u2010G of which 10 displayed characteristic anchor residues. As compared to the response in short\u2010term (6\u2009h) assays to immunodominant IE\u20101 and pp65 antigens, none of the HLA\u2010G\u2010binding peptides stimulated cytokine production by CD8+ T cells from HCMV\u2010seropositive blood donors (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915). Following a 14\u2010day peptide stimulation of PBMC and expansion with IL\u20102, CD8+ T cells specifically responding to a subset of these viral antigens were detected in some individuals, yet were not restricted by HLA\u2010G in functional assays. A subset of viral peptides did bind to both HLA\u2010G and \u2010E but were not recognised by CD94\/NKG2 NK cell receptors. Our results provide the first evidence that HLA\u2010G may display potentially immunogenic viral peptides in HCMV\u2010infected cells, yet do not support their ability to promote HLA\u2010G\u2010restricted CD8+ T cell responses nor to modulate NK cell functions.\n                  <\/jats:p>","DOI":"10.1111\/tan.70089","type":"journal-article","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T05:42:50Z","timestamp":1746855770000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human Cytomegalovirus Antigen Presentation by\n                    <scp>HLA<\/scp>\n                    \u2010G in Infected Cells"],"prefix":"10.1111","volume":"105","author":[{"given":"Mireia","family":"Altadill","sequence":"first","affiliation":[{"name":"Department of Medicine and Life Sciences University Pompeu Fabra  Barcelona 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Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Vilches","sequence":"additional","affiliation":[{"name":"Immunogenetics and Histocompatibility Lab, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro \u2010 Segovia de Arana  Madrid Spain"},{"name":"Organizaci\u00f3n Nacional de Trasplantes, Ministerio de Sanidad  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hartmut","family":"Hengel","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine, University of Freiburg  Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Halenius","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine, University of Freiburg  Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-065X","authenticated-orcid":false,"given":"Miguel","family":"L\u00f3pez\u2010Botet","sequence":"additional","affiliation":[{"name":"Department of Medicine and Life Sciences University Pompeu Fabra  Barcelona Spain"},{"name":"Hospital del Mar Research Institute  Barcelona 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