ArticleBlood2023
HLA-E-restricted immune responses are crucial for the control of EBV infections and the prevention of PTLD.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- Epstein-Barr Virus and Multiple Sclerosis: Mechanistic Insights into Virus-Driven Autoimmunity.Microorganisms · 2026Review
- Polyclonal evolution of lymphoproliferative disorders in XLP1.Journal of human immunity · 2026Article
- EBV Genome Variations and Association With Diseases.Journal of medical virology · 2026Review
- ImmuSeeker: deep mining of immune-related gene family signatures through lineage reconstruction.Genome biology · 2026Article
- NKG2A+ NK cell cytotoxicity of Epstein-Barr virus infected B cells is mediated through the NKG2D and NKp30 activating receptors.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Targeting MHC-E as a new strategy for vaccines and immunotherapeutics.Nature reviews. Immunology · 2026Review
- The immunosuppressive tumor microenvironment in post-transplant lymphoproliferative disorder: pathogenesis and novel therapeutic frontiers.Frontiers in immunology · 2026Review
- Epstein-Barr virus-associated tumors: commonalities in pathogenesis and the tumor immune microenvironment.Frontiers in immunology · 2026Review
- Predictive biomarkers and preventive strategies for PTLD: a turning point in viro-immunologic precision medicine?Transplant international : official journal of the European Society for Organ Transplantation · 2026Review
- Herpesvirus-host interactions in neurological diseases: the immunogenetic role of HLA-E.Journal of virology · 2025Review
- A cytoplasmic motif in HLA-E that drives clathrin-mediated endocytosis and VCP-associated postendocytic trafficking.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HLA matching or CRISPR editing of HLA class I/II enables engraftment and effective function of allogeneic human regulatory T cell therapy in a humanized mouse transplantation model.Nature communications · 2025Article
- Investigation ofInternational journal of molecular sciences · 2025Article
- Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation.Orphanet journal of rare diseases · 2025Article
- HLA-E/peptide complexes differentially interact with NKG2A/CD94 and T cell receptors.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- HLA-E: Immune Receptor Functional Mechanisms Revealed by Structural Studies.Immunological reviews · 2025Review
- The diagnostic value of lymphocyte profiling for infectious mononucleosis and mycoplasma pneumoniae pneumonia.Frontiers in pediatrics · 2025Article
- The diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis.BMC pediatrics · 2024Article
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6 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Primary Epstein-Barr virus (EBV) infections may cause infectious mononucleosis (IM), whereas EBV reactivations in solid organ and hematopoietic stem cell transplant recipients are associated with posttransplantation lymphoproliferative disorders (PTLDs). It is still unclear why only a minority of primary EBV-infected individuals develop IM, and why only some patients progress to EBV+PTLD after transplantation. We now investigated whether nonclassic human leukocyte antigen E (HLA-E)-restricted immune responses have a significant impact on the development of EBV diseases in the individual host. On the basis of a large study cohort of 1404 patients and controls as well as on functional natural killer (NK) and CD8+ T-cell analyses, we could demonstrate that the highly expressed HLA-E∗0103/0103 genotype is protective against IM, due to the induction of potent EBV BZLF1-specific HLA-E-restricted CD8+ T-cell responses, which efficiently prevent the in vitro viral dissemination. Furthermore, we provide evidence that the risk of symptomatic EBV reactivations in immunocompetent individuals as well as in immunocompromised transplant recipients depends on variations in the inhibitory NKG2A/LMP-1/HLA-E axis. We show that EBV strains encoding for the specific LMP-1 peptide variants GGDPHLPTL or GGDPPLPTL, presented by HLA-E, elicit strong inhibitory NKG2A+ NK and CD8+ T-cell responses. The presence of EBV strains encoding for both peptides was highly associated with symptomatic EBV reactivations. The further progression to EBV+PTLD was highly associated with the presence of both peptide-encoding EBV strains and the expression of HLA-E∗0103/0103 in the host. Thus, HLA-E-restricted immune responses and the NKG2A/LMP-1/HLA-E axis are novel predictive markers for EBV+PTLD in transplant recipients and should be considered for future EBV vaccine design.
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