ArticleImmunogenetics2016
The diversity of the HLA-E-restricted peptide repertoire explains the immunological impact of the Arg107Gly mismatch.
Article in Immunogenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Donor HLA-E Status Associates with Disease-Free Survival and Transplant-Related Mortality after Non In Vivo T Cell-Depleted HSCT for Acute Leukemia.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019Trial
- Article
- MHC Attention: Identifying HLA-E presented cancer antigens through deep learning and high-throughput screening.bioRxiv : the preprint server for biology · 2026Article
- Innovative CRISPR/Cas9-Based Strategy for Allele-Specific HLA Peptidome Analysis Using a Pan-HLA Antibody.Molecular & cellular proteomics : MCP · 2026Article
- Nonclassical MHC-I Molecules: Emerging Therapeutic Targets in Next-Generation Immunotherapy.MedComm · 2026Review
- HLA-E as an Emerging Checkpoint and Biomarker in Personalized Cancer Immunotherapy.Current medical science · 2026Review
- Targeting MHC-E as a new strategy for vaccines and immunotherapeutics.Nature reviews. Immunology · 2026Review
- Herpesvirus-host interactions in neurological diseases: the immunogenetic role of HLA-E.Journal of virology · 2025Review
- The Expanding Role of HLA-E in Host Defense: A Target for Broadly Applicable Vaccines and Immunotherapies.Cells · 2025Review
- Full-length gene polymorphism of the non-classical HLA-E in Estonian individuals.Immunogenetics · 2025Article
- HLA-E: Immune Receptor Functional Mechanisms Revealed by Structural Studies.Immunological reviews · 2025Review
- CD8Science advances · 2024Article
- An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Instability of the HLA-E peptidome of HIV presents a major barrier to therapeutic targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Deciphering the HLA-E immunopeptidome with mass spectrometry: an opportunity for universal mRNA vaccines and T-cell-directed immunotherapies.Frontiers in immunology · 2024Review
- NK cell education: Physiological and pathological influences.Frontiers in immunology · 2023Review
- Identification of HLA-E BindingJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Engineering of immune checkpoints B7-H3 and CD155 enhances immune compatibility of MHC-ICell reports · 2022Article
- Disruption of the HLA-E/NKG2X axis is associated with uncontrolled HIV infections.Frontiers in immunology · 2022Article
- What a Difference an Amino Acid Makes: An All-Atom Simulation Study of Nonameric Peptides in Inhibitory HLA-E/NKG2A/CD94 Immune Complexes.Frontiers in pharmacology · 2022Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human leukocyte antigen (HLA)-E molecules are potent inhibitors of NK cell-mediated killing. Low in polymorphisms, two alleles are widely expressed among diverse populations: HLA-E*01:01 and HLA-E*01:03. Both alleles are distinguished by one SNP resulting in the substitution Arg107Gly. Both alleles present a limited set of peptides derived from class I leader sequences physiologically; however, HLA-E*01:01 presents non-canonical peptides in the absence of HLA class I molecules. To further assess the functional differences between both alleles, we analyzed the peptide repertoire of HLA-E*01:03 by applying soluble HLA technology followed by mass-spectrometric peptide sequencing. HLA-E*01:03 restricted peptides showed a length of 9-17 amino acids and differed in their biophysical properties, no overlap in the peptide repertoire of both allelic variants could be observed; however, both alleles shared marginal peptides from the same proteomic content. Artificial APCs expressing empty HLA-E*01:01 or E*01:03 molecules were generated and stabilized using cognate HLA class I-derived peptide ligands to analyze the impact of residue 107 within the HLA-E heavy chain on the NKG2/CD94 receptor engagement. Differences in peptide stabilization could be translated to the density and half-life time of peptide-HLA-E molecules on the cell surface that subsequently impacted NK cell inhibition as verified by cytotoxicity assays. Taken together, these data illustrate functional differences of HLA-E allelic variants induced by a single amino acid. Furthermore, the function of HLA-E in pathophysiologic situations when the HLA processing machinery is interrupted seems to be more emphasized than previously described, implying a crucial role for HLA-E in tumor or viral immune episodes.
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