ArticlePloS one2015
Cell surface expression level variation between two common Human Leukocyte Antigen alleles, HLA-A2 and HLA-B8, is dependent on the structure of the C terminal part of the alpha 2 and the alpha 3 domains.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Recruiting ESCRT to single-chain heterotrimer peptide MHCI releases antigen-presenting vesicles that stimulate T cells selectively.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Specific Instability of HLA-A*03:01 Expression in HEK-293 Cells.International journal of molecular sciences · 2025Article
- Extracellular Vesicles as Precision Delivery Systems for Biopharmaceuticals: Innovations, Challenges, and Therapeutic Potential.Pharmaceutics · 2025Review
- Dual role of the peptide-loading complex as proofreader and limiter of MHC-I presentation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Gemcitabine Modulates HLA-I Regulation to Improve Tumor Antigen Presentation by Pancreatic Cancer Cells.International journal of molecular sciences · 2024Article
- Endogenous H3.3K27M derived peptide restricted to HLA-A∗02:01 is insufficient for immune-targeting in diffuse midline glioma.Molecular therapy oncolytics · 2023Article
- Functional antigen processing and presentation mechanism as a prerequisite factor of response to treatment with dendritic cell vaccines and anti-PD-1 in preclinical murine LLC1 and GL261 tumor models.Cancer immunology, immunotherapy : CII · 2022Article
- HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation.Frontiers in immunology · 2022Review
- Specific Class I HLA Supertypes but Not HLA Zygosity or Expression Are Associated with Outcomes following HLA-Matched Allogeneic Hematopoietic Cell Transplant: HLA Supertypes Impact Allogeneic HCT Outcomes.Transplantation and cellular therapy · 2021Article
- Gene signature of antigen processing and presentation machinery predicts response to checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma.Journal for immunotherapy of cancer · 2020Article
- Targeting the coding sequence: opposing roles in regulating classical and non-classical MHC class I molecules by miR-16 and miR-744.Journal for immunotherapy of cancer · 2020Article
- The Genetic Mechanisms Driving Diversification of theFrontiers in immunology · 2020Review
- Data-Independent Acquisition of HLA Class I Peptidomes on the Q Exactive Mass Spectrometer Platform.Proteomics · 2017Article
- Sequence and Phylogenetic Analysis of the Untranslated Promoter Regions forJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- Article
- Autologous and Allogenous Antibodies in Lung and Islet Cell Transplantation.Frontiers in immunology · 2016Review
- Alloantibody Generation and Effector Function Following Sensitization to Human Leukocyte Antigen.Frontiers in immunology · 2016Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses. Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of-B7 (P = 0.002). Transfection experiments with full-length HLA-A2 and -B8 encoding plasmids confirmed this (54,031 molecules per cell vs. 2,466, respectively, P = 0.001) independently of transcript levels suggesting a post-transcriptional regulation. Using chimeric constructs we found that the cytoplasmic tail and the transmembrane region had no impact on the differential cell surface expression. In contrast, ~65% of the difference could be mapped to the six C-terminal amino acids of the alpha 2 domain and the alpha 3 domain (amino acids 176-284), i.e. amino acids not previously shown to be of importance for differential expression levels of HLA class I molecules. We suggest that the differential cell surface expression of two common HLA-A and-B alleles is regulated by a post-translational mechanism that may involve hitherto unrecognized molecules.
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