ArticleProceedings of the National Academy of Sciences of the United States of America1998
HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 405 papers.
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Who cites it
405 citing papers in PubMed, 1,034 citations in OpenAlex.
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- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- HLA-E single-chain trimer shields gene-edited allogeneic CAR T cells from NK cell attack.Blood advances · 2026Article
- CRISPR-Cas9-mediated knock-in of cytomegalovirus US2 provides an alternative strategy for generating hypoimmunogenic hiPSC lines.Scientific reports · 2026Article
- MHC Attention: Identifying HLA-E presented cancer antigens through deep learning and high-throughput screening.bioRxiv : the preprint server for biology · 2026Article
- Circumventing IFN-γ induced resistance in ovarian cancer with a double-hit: NKG2A knockout of PRAME-TCR expressing NK cells.Journal of ovarian research · 2026Article
- Nonclassical MHC-I Molecules: Emerging Therapeutic Targets in Next-Generation Immunotherapy.MedComm · 2026Review
- Exercise-mobilized lymphocytes enhance the function of cytokine-induced memory-like NK cells against myeloid leukemia.Blood advances · 2026Article
- HLA-E as an Emerging Checkpoint and Biomarker in Personalized Cancer Immunotherapy.Current medical science · 2026Review
- The CD94/NKG2A-HLA-E Axis as a Target in Cancer Immunotherapy: A Critical Perspective.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- 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
- Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy.Cell stem cell · 2026Review
- Targeting MHC-E as a new strategy for vaccines and immunotherapeutics.Nature reviews. Immunology · 2026Review
- Interaction between HLA-B leader peptide variants and cytomegalovirus serostatus is associated with early T cell-mediated rejection in kidney transplantation.Frontiers in immunology · 2026Article
- Shared HLA-E and Mamu-E Peptide Repertoires With Subtle Peptide Binding Differences Revealed by Combined nDSF- and Fluorescence Polarisation-Based Methods.European journal of immunology · 2026Article
- Beyond KIR and NKG2A blockade: reprogramming NK-cell immunity in solid tumors.Frontiers in cell and developmental biology · 2026Review
- The gamma delta T/NK cell product GADEKILL as a novel immunotherapeutic tool for neuroblastoma patients: role of B7H6 and BTN2A1 in tumor cell killing.Frontiers in immunology · 2026Article
- Mechanism by which SAHA regulates HLA-E expression via the endoplasmic reticulum stress-related PERK/ATF4/CHOP pathway in neuroblastoma.Frontiers in immunology · 2026Article
- Methods for Probing NK Cell Surveillance of Antigen Presentation.Methods in molecular biology (Clifton, N.J.) · 2026Article
345 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
We previously showed that the availability of a nonamer peptide derived from certain HLA class I signal sequences is a necessary requirement for the stabilization of endogenous HLA-E expression on the surface of 721.221 cells. This led us to examine the ability of HLA-E to protect HLA class I transfectants from natural killer (NK) cell-mediated lysis. It was possible to implicate the CD94/NKG2A complex as an inhibitory receptor recognizing this class Ib molecule by using as target a .221 transfectant selectively expressing surface HLA-E. HLA-E had no apparent inhibitory effect mediated through the identified Ig superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1. Further studies of CD94/NKG2+ NK cell-mediated recognition of .221 cells transfected with different HLA class I allotypes (i.e., -Cw4, -Cw3, -B7) confirmed that the inhibitory interaction was mediated by CD94/NKG2A recognizing the surface HLA-E molecule, because only antibodies directed against either HLA-E, CD94, or CD94/NKG2A specifically restored lysis. Surface stabilization of HLA-E in cold-treated .221 cells loaded with appropriate peptides was sufficient to confer protection, resulting from recognition of the HLA class Ib molecule by the CD94/NKG2A inhibitory receptor. Consistent with the prediction that the ligand for CD94/NKG2A is expressed ubiquitously, our examination of HLA-E antigen distribution indicated that it is detectable on the surface of a wide variety of cell types.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.