Affinage

HLA-G

HLA class I histocompatibility antigen, alpha chain G · UniProt P17693

Length
338 aa
Mass
38.2 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HLA-G is a nonclassical MHC class Ib molecule that establishes immune tolerance by delivering inhibitory signals to NK cells, T cells, and myeloid cells, a role first demonstrated when HLA-G expression rendered target cells resistant to lysis by decidual NK cells (PMID:8181068) and was extended to inhibition of allogeneic T-cell proliferation and antigen-specific CTL responses (PMID:10092545). Tolerance is executed through engagement of inhibitory receptors: membrane-bound HLA-G1 binds ILT2 and ILT4 to suppress NK- and T-cell cytolysis, while secreted HLA-G5 binds CD8 to trigger Fas/FasL-mediated apoptosis of activated CD8+ lymphocytes, and engagement of KIR2DL4 produces context-dependent outcomes (PMID:14708711); KIR2DL4 ligation can additionally drive NK senescence with a pro-angiogenic secretory phenotype supporting vascular remodeling (PMID:24998350). Crystallographic analysis shows HLA-G binds a constrained nine-residue self-peptide and forms disulfide-bonded dimers in an oblique conformation consistent with a 1:2 dimer:receptor stoichiometry, providing the structural basis for differential LIR-1/LIR-2 affinity (PMID:17400055), and surface delivery of HLA-G1 and HLA-G5 requires peptide loading via TAP-dependent or TAP-independent routes (PMID:12440768). Beyond immune inhibition, soluble HLA-G5 suppresses endothelial proliferation, migration, and angiogenesis through CD160 (PMID:17467060), and HLA-G expands tolerance by inducing durable suppressor T cells and by transferring itself to effector cells through trogocytosis (PMID:17881247). Its restricted expression is enforced at multiple levels: a promoter that lacks the ISRE and carries modified enhancer A/SXY modules, making it unresponsive to NF-κB, IRF1, and CIITA (PMID:11797094); CpG methylation of its 5' regulatory region that silences the gene and is reversible by demethylating agents and HDAC inhibitors (PMID:12552087, PMID:15514928); and post-transcriptional repression by miR-148a/miR-152 binding the 3'UTR, which when relieved restores ILT2-mediated NK inhibition (PMID:22438923). Inducible expression is driven by IFN-γ at the transcriptional level (PMID:8666791, PMID:11137212), while the short cytoplasmic tail impairs endocytosis and sustains surface display (PMID:9368631). HLA-G is a physiological hallmark of extravillous trophoblasts whose subtypes differ in capacity to induce regulatory T cells (PMID:32581122), and its tolerogenic axis has been exploited therapeutically by anti-HLA-G CAR-T cells that resist ILT2-mediated inhibition by HLA-G+ tumors (PMID:33737343).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 Medium

    Established that a nonclassical class I molecule, not classical HLA, can shield cells from NK-mediated killing, defining HLA-G's core tolerogenic function.

    Evidence NK cytotoxicity assay on HLA-G transfectants of HLA-null 721.221 cells against decidual and peripheral NK effectors

    PMID:8181068

    Open questions at the time
    • Did not identify the inhibitory receptor mediating protection
    • Limited to NK cytolysis, not other immune effectors
  2. 1996 Medium

    Showed HLA-G is inducible rather than strictly constitutive, with IFN-γ selectively upregulating it in myeloid cells.

    Evidence Northern blot, RT-PCR, flow cytometry on macrophage lines and monocytes treated with interferons

    PMID:8666791

    Open questions at the time
    • Did not map the cis-elements or transcription factors mediating IFN-γ response
    • Mechanism of IFN-γ specificity over IFN-α/β unresolved
  3. 1997 High

    Explained how HLA-G is retained at the cell surface, attributing impaired endocytosis to its short cytoplasmic tail.

    Evidence Flow cytometry endocytosis assay with chimeric HLA-C/HLA-G constructs and non-perturbative β2m label-exchange tracking

    PMID:9368631

    Open questions at the time
    • Did not identify the trafficking machinery bypassed
    • Did not address differential trafficking of soluble vs membrane isoforms
  4. 1999 Medium

    Broadened HLA-G's inhibitory reach beyond NK cells to T-cell proliferation and CTL responses, and to a tumor (melanoma) context.

    Evidence In vitro NK and T-cell assays with HLA-G1/G2 transfectants and soluble HLA-G; NK assays with HLA-G+ melanoma lines

    PMID:10092545 PMID:10479054

    Open questions at the time
    • Receptors mediating T-cell inhibition not yet defined
    • Distinction between membrane and soluble isoform mechanisms incomplete
  5. 2000 Medium

    Confirmed IFN-γ induction operates at the transcriptional level in primary epithelial tissues beyond myeloid cells.

    Evidence Flow cytometry and RT-PCR in primary thymic and amnion epithelial cells treated with IFN-γ

    PMID:11137212

    Open questions at the time
    • Promoter elements responsible not mapped
    • No link to physiological signals driving induction in vivo
  6. 2001 Medium

    Defined the cis-regulatory basis of HLA-G's restricted expression, showing its promoter is refractory to canonical class I inducers.

    Evidence Promoter sequence analysis and transgenic HLA-G mouse models with in situ hybridization/RT-PCR

    PMID:11797094

    Open questions at the time
    • Did not reconcile promoter unresponsiveness with documented IFN-γ inducibility
    • Positive activators driving tissue-specific expression not identified
  7. 2002 Medium

    Showed peptide loading is a quality-control checkpoint for surface delivery of both membrane and soluble HLA-G, using TAP-dependent and -independent routes.

    Evidence Biochemical trafficking studies using viral US-protein immune-escape tools

    PMID:12440768

    Open questions at the time
    • Identity of bound peptides not defined here
    • TAP-independent loading mechanism not detailed
  8. 2003 Medium

    Identified the inhibitory receptor partners (ILT2, ILT4, CD8, KIR2DL4) and resolved that soluble HLA-G5 kills CD8+ cells via Fas/FasL.

    Evidence In vitro receptor-binding, cytotoxicity, and apoptosis assays with HLA-G isoforms

    PMID:14708711

    Open questions at the time
    • KIR2DL4 outcome dependence on activation state not mechanistically resolved
    • Quantitative receptor affinities not established
  9. 2003 High

    Established DNA methylation as the dominant epigenetic switch silencing HLA-G, reversible to drive surface expression.

    Evidence 5-aza-2'-deoxycytidine and HDAC-inhibitor treatment of seven HLA-G-negative lines with RT-PCR/flow cytometry; bisulfite sequencing and ChIP in melanoma/choriocarcinoma lines

    PMID:12552087 PMID:15514928

    Open questions at the time
    • Did not identify methyltransferases/demethylases regulating the locus in vivo
    • Role of the putative -1.2 kb locus control region not functionally dissected
  10. 2005 Medium

    Demonstrated that truncated HLA-G isoforms from the G*0105N null allele retain surface expression and NK-protective function, expanding the functional repertoire beyond HLA-G1/G5.

    Evidence Transfection of genomic HLA-G*0105N and NK cytotoxicity assay

    PMID:15814900

    Open questions at the time
    • Receptors engaged by alternative isoforms not defined
    • Physiological relevance in null-allele carriers not addressed
  11. 2006 High

    Provided the structural basis for HLA-G receptor selectivity, revealing a constrained self-peptide and a disulfide-bonded dimer implying 1:2 receptor stoichiometry.

    Evidence X-ray crystallography of HLA-G

    PMID:17400055

    Open questions at the time
    • No co-crystal with ILT/KIR receptors
    • Dimer contribution to in vivo signaling not directly tested
  12. 2007 Medium

    Extended HLA-G function to anti-angiogenesis via CD160 and to active spread of tolerance through suppressor-cell induction and trogocytosis, with tumor microenvironment cues regulating its expression.

    Evidence Endothelial proliferation/migration/tubule and in vivo rabbit corneal angiogenesis assays; T-cell differentiation and trogocytosis assays; hypoxia/IDO/TNF-α stimulation; OVCAR-3 transfectant NK assays with mAb 87G blocking

    PMID:17467060 PMID:17846022 PMID:17881247

    Open questions at the time
    • Mechanistic link between CD160 binding and endothelial apoptosis incomplete
    • Durability and in vivo relevance of trogocytosis-derived suppressors unclear
  13. 2012 High

    Identified post-transcriptional control by miR-148a/miR-152 and tied it functionally to NK inhibition, explaining tissue-specific high expression in placenta.

    Evidence miRNA gain/loss, 3'UTR luciferase reporter, NK killing and LILRB1 recognition assays, plus tissue miRNA profiling

    PMID:22438923

    Open questions at the time
    • Upstream regulation of these miRNAs not addressed
    • Interaction with methylation-based control not integrated
  14. 2014 Medium

    Linked KIR2DL4-HLA-G engagement to NK senescence and a pro-angiogenic secretory phenotype supporting pregnancy vascular remodeling, expanding HLA-G beyond simple inhibition.

    Evidence Review of NK senescence assays and SASP cytokine secretion readouts from KIR2DL4-HLA-G studies

    PMID:24998350

    Open questions at the time
    • Primary data summarized in a review, not original here
    • Signaling pathway from KIR2DL4 to senescence not detailed
  15. 2020 Medium

    Resolved heterogeneity among HLA-G+ extravillous trophoblasts, showing subtype-specific capacity to induce regulatory T cells in maternal-fetal tolerance.

    Evidence Primary EVT purification, phenotyping, gene expression profiling, and Treg induction co-cultures

    PMID:32581122

    Open questions at the time
    • Molecular determinants of subtype Treg-inducing capacity not defined
    • Causal role of HLA-G itself in Treg induction not isolated from other EVT factors
  16. 2021 Medium

    Demonstrated therapeutic exploitation of the HLA-G axis with CAR-T cells that resist ILT2 inhibition and avoid exhaustion against HLA-G+ tumors.

    Evidence Anti-HLA-G CAR-T cytotoxicity, in vivo tumor control, ILT2-inhibition, and memory phenotype assays

    PMID:33737343

    Open questions at the time
    • On-target/off-tumor effects in HLA-G+ healthy tissue not assessed
    • Clinical efficacy not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the layered regulatory inputs (promoter architecture, CpG methylation, miRNAs, IFN-γ, progesterone) are integrated to produce the precise tissue- and context-specific expression of HLA-G remains unresolved.
  • No unified model linking epigenetic, transcriptional, and post-transcriptional control
  • Positive transcriptional activators driving constitutive trophoblast expression unidentified
  • In vivo receptor-engagement stoichiometry and signaling outputs incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-1500931 Cell-Cell communication 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CD160CD8KIR2DL4LILRB1LILRB2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 HLA-G expression on trophoblast cells confers resistance to lysis by decidual NK cells. HLA-G transfectants of HLA-null LCL 721.221 cells were protected from NK effectors isolated from decidua or peripheral blood, demonstrating that a nonclassical Class I HLA molecule provides NK resistance. NK cytotoxicity assay using HLA-G transfectants of HLA-null LCL 721.221 cells Cellular immunology Medium 8181068
1996 IFN-γ selectively induces HLA-G expression in mononuclear phagocytes (macrophage cell lines and blood monocytes) at both mRNA and protein levels, increasing cell-surface and intracellular HLA-G in a dose-dependent manner, whereas IFN-α and IFN-β are poor inducers of cell-surface HLA-G protein. Northern blot hybridization, RT-PCR, immunohistochemistry, flow cytometry on macrophage cell lines (U937, HL-60, THP-1) and blood monocytes treated with interferons Journal of immunology Medium 8666791
1997 HLA-G undergoes severely impaired spontaneous endocytosis compared to classical MHC class I proteins, attributable to its short cytoplasmic tail. Chimeric proteins with HLA-C extracellular domains fused to the HLA-G C-terminal sequence, or GPI-tailed HLA-C proteins, were also not efficiently internalized, confirming the cytoplasmic tail as the determinant. Flow cytometry-based endocytosis assay using antibody-labeled transfectants; mutant β2-microglobulin (Ser88Cys) fluorescent-label exchange method to track internalization non-perturbatively European journal of immunology High 9368631
1999 HLA-G inhibits NK cell cytolysis and T cell allogeneic proliferative and antigen-specific CTL responses. Membrane-bound HLA-G1 and HLA-G2 transfected cells, as well as full-length soluble HLA-G, were shown to impair NK and T cell functions in vitro. In vitro NK cytotoxicity assays and T cell allogeneic proliferation/CTL assays using HLA-G1- and HLA-G2-transfected cells and soluble HLA-G protein Seminars in cancer biology Medium 10092545
1999 HLA-G expressed on melanoma cells inhibits NK cell cytolysis. HLA-G-positive melanoma cell lines inhibited lysis by the NK cell line YT2C2-PR, and this inhibition occurred through interaction with inhibitory receptors distinct from known KIRs recognizing HLA-E or classical class I molecules. RT-PCR for HLA-G transcripts in melanoma cell lines and biopsies; NK cytotoxicity assay using YT2C2-PR NK cells against HLA-G-positive melanoma lines Journal of reproductive immunology Medium 10479054
2000 IFN-γ re-induces HLA-G cell surface expression and upregulates HLA-G transcripts in primary thymic epithelial cell (TEC) and amnion epithelial cell cultures, demonstrating that IFN-γ induction is mediated at the transcriptional level in these tissues. Flow cytometry for HLA-G surface expression; RT-PCR for HLA-G transcripts in primary thymic and amnion epithelial cell cultures treated with IFN-γ Human immunology Medium 11137212
2001 The HLA-G promoter lacks the ISRE element and contains modified enhancer A and SXY modules, rendering it unresponsive to NF-κB, IRF1, and class II transactivator (CIITA) DNA-binding factors, explaining its restricted tissue-specific expression. Promoter sequence analysis; transgenic HLA-G mouse models with in situ hybridization and RT-PCR to assess constitutive placental expression Immunogenetics Medium 11797094
2002 Membrane-bound HLA-G1 and soluble HLA-G5 both require peptide association for cell surface expression, utilizing TAP-dependent or TAP-independent pathways. Peptide loading plays a critical role in controlling the quality of HLA-G molecules reaching the cell surface. Surface expression of truncated HLA-G isoforms is also possible. Biochemical trafficking studies and analysis of viral immune escape strategies (US proteins); biochemical fractionation and protein expression analysis Cellular and molecular life sciences Medium 12440768
2003 HLA-G gene repression is mediated by DNA methylation of CpG sites in its 5' regulatory region. Treatment of HLA-G-negative cell lines with histone deacetylase inhibitors or the demethylating agent 5-aza-2'-deoxycytidine reverses this repression and can directly induce HLA-G cell-surface expression. Pharmacological demethylation (5-aza-2'-deoxycytidine) and histone deacetylase inhibitor treatment of seven HLA-G-negative cell lines; RT-PCR and flow cytometry for HLA-G expression Proceedings of the National Academy of Sciences of the United States of America High 12552087
2003 HLA-G1 binds inhibitory receptors ILT2 and ILT4, inhibiting NK- and T-cell-mediated lysis of target cells. Secreted HLA-G5 binds CD8 and induces Fas/FasL-mediated apoptosis in activated CD8+ lymphocytes. Engaging KIR2DL4 triggers different reactions depending on the activation state of effector cells. In vitro receptor-binding and cytotoxicity assays; apoptosis assays with soluble HLA-G5 and CD8+ lymphocytes Seminars in cancer biology Medium 14708711
2003 HLA-G is expressed in the cornea (keratocytes, epithelial cells, and endothelial cells) of both healthy and pathologic tissue, with transcript splicing pattern consistent with other HLA-G-expressing tissues, suggesting a role in maintaining immune privilege of the cornea. Immunohistochemistry with anti-HLA-G monoclonal antibody; RT-PCR for HLA-G transcripts on cryopreserved corneal sections Human immunology Low 14602233
2005 HLA-G gene silencing in tumor cells is caused by CpG site hypermethylation within a 450-bp 5' regulatory region upstream of the start codon, and activation upon demethylation correlates with histone acetylation status within this region and a putative locus control region at -1.2 kb. Bisulfite sequencing/methylation analysis of HLA-G 5' regulatory region in melanoma and choriocarcinoma cell lines; chromatin immunoprecipitation for histone acetylation; 5-aza-2'-deoxycytidine treatment International journal of cancer High 15514928
2005 The HLA-G*0105N null allele, which has a single base deletion preventing translation of HLA-G1, HLA-G4, and HLA-G5, can generate alternative isoforms (HLA-G2, G3, G6, G7) that are expressed on the cell surface and retain the ability to protect against NK cell lysis. Cloning of genomic HLA-G*0105N DNA; transfection into HLA-class I-positive human cell line; NK cytotoxicity assay Biology of reproduction Medium 15814900
2006 The crystal structure of HLA-G reveals a nine-residue self-peptide bound in a constrained mode within the peptide-binding cleft (similar to HLA-E). The α3 domain is structurally distinct from class Ia MHC molecules, providing a structural basis for observed differences in affinity for LIR-1 and LIR-2. A disulfide-bonded dimer adopts an oblique conformation suggesting a 1:2 (HLA-G dimer:receptor) complex stoichiometry, and the dimer orientation makes KIR2DL4 binding via dimerization unlikely. X-ray crystallography of HLA-G Human immunology High 17400055
2007 HLA-G expression on ovarian carcinoma cells (OVCAR-3 transfectants) directly inhibits NK-92 cell lysis, and this inhibition can be restored by the anti-HLA-G conformational monoclonal antibody 87G. HLA-G cloning and expression in OVCAR-3 cells; NK-92 cytotoxicity assay; antibody-blocking experiment with mAb 87G Annals of oncology Medium 17846022
2007 Soluble HLA-G1 (HLA-G5) inhibits endothelial cell proliferation, migration, and tubule formation through binding to the CD160 receptor via an apoptotic pathway, and blocks in vivo rabbit corneal neoangiogenesis. In vitro endothelial cell proliferation, migration and tubule formation assays with soluble HLA-G1; receptor binding to CD160; in vivo rabbit corneal angiogenesis model Journal of reproductive immunology Medium 17467060
2007 HLA-G induces suppressor cells via two distinct processes: (i) differentiation of naïve T cells into lasting suppressor T cells, and (ii) rapid transfer of HLA-G from APCs or tumor cells to T or NK cells via trogocytosis, converting them into temporary HLA-G-positive suppressor cells. Tumor microenvironment factors including hypoxia, IDO, and TNF-α regulate HLA-G expression by tumor cells. In vitro T cell differentiation assays; trogocytosis experiments; hypoxia/IDO/TNF-α stimulation of tumor cells with HLA-G expression readout Seminars in cancer biology Medium 17881247
2009 Progesterone upregulates HLA-G expression (both cell-surface and cytoplasmic) in mesenchymal stem cells (MSCs) isolated from adipose tissue, bone marrow, and decidua, at both protein and mRNA levels. MSC culture with progesterone; flow cytometry and RT-PCR for HLA-G expression American journal of reproductive immunology Low 19527229
2012 miR-148a and miR-152 down-regulate HLA-G expression by directly binding its 3'UTR, and this down-regulation abolishes LILRB1 (ILT2)-mediated inhibition of NK cell killing. In placenta, both miRNAs are expressed at relatively low levels compared to other tissues, which may enable tissue-specific high HLA-G expression. miRNA overexpression/inhibition experiments; 3'UTR luciferase reporter assay; NK cell killing assay; LILRB1 recognition assay; miRNA and HLA-G mRNA expression profiling in placenta vs. other tissues PloS one High 22438923
2014 KIR2DL4-HLA-G interaction induces cellular senescence in NK cells, and the resulting senescence-associated secretory phenotype (SASP) promotes secretion of pro-angiogenic factors that drive vascular remodeling during pregnancy. Review of experimental data on KIR2DL4-HLA-G interactions, NK cell senescence assays, and cytokine secretion readouts (senescence-associated secretory phenotype) Cellular & molecular immunology Medium 24998350
2020 Three distinct types of HLA-G+ extravillous trophoblasts (EVT) can be purified from the placental disk and chorionic membrane; these EVT subtypes have unique phenotypes, gene expression profiles, and differing capacities to induce regulatory T cells (Treg) in co-culture, with gestational age and fetal sex influencing EVT biology. Primary cell purification and culture of HLA-G+ EVT from term and first trimester placenta; phenotypic characterization by flow cytometry; gene expression profiling; Treg induction co-culture assays Proceedings of the National Academy of Sciences of the United States of America Medium 32581122
2021 Anti-HLA-G CAR-T cells are cytotoxic against HLA-G+ tumor cells in vitro and can control and eliminate HLA-G+ tumors in vivo. These CAR-T cells are insensitive to ILT2-mediated inhibition by tumor-expressed HLA-G and differentiate into long-term memory effector cells without functional exhaustion upon repeated stimulation. Generation of third-generation CAR-T cells with anti-HLA-G monoclonal antibodies; in vitro cytotoxicity assays; in vivo tumor control experiments; ILT2-inhibition assays; memory phenotype analysis Journal for immunotherapy of cancer Medium 33737343

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 HLA-G and immune tolerance in pregnancy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 358 15857883
2015 HLA-G: An Immune Checkpoint Molecule. Advances in immunology 335 26073983
2003 HLA-G molecules: from maternal-fetal tolerance to tissue acceptance. Advances in immunology 267 14711057
2010 Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association. Cellular and molecular life sciences : CMLS 261 21107637
2005 HLA-G in human reproduction: aspects of genetics, function and pregnancy complications. Human reproduction update 227 16280356
2003 Expression of HLA-G in human cornea, an immune-privileged tissue. Human immunology 213 14602233
2017 HLA-G: At the Interface of Maternal-Fetal Tolerance. Trends in immunology 211 28279591
1996 Expression of HLA-G in human mononuclear phagocytes and selective induction by IFN-gamma. Journal of immunology (Baltimore, Md. : 1950) 193 8666791
1994 Resistance of HLA-G and HLA-A2 transfectants to lysis by decidual NK cells. Cellular immunology 172 8181068
2008 A critical look at HLA-G. Trends in immunology 160 18538632
2012 The immunosuppressive molecule HLA-G and its clinical implications. Critical reviews in clinical laboratory sciences 154 22537084
2007 Soluble HLA-G: Are they clinically relevant? Seminars in cancer biology 147 17825579
1999 The functionality of HLA-G is emerging. Immunological reviews 143 10319265
2014 Transcriptional and posttranscriptional regulations of the HLA-G gene. Journal of immunology research 132 24741620
2003 HLA-G gene repression is reversed by demethylation. Proceedings of the National Academy of Sciences of the United States of America 132 12552087
2020 Roles of HLA-G in the Maternal-Fetal Immune Microenvironment. Frontiers in immunology 128 33193435
2012 MiRNA-mediated control of HLA-G expression and function. PloS one 128 22438923
2018 Heterogeneity of HLA-G Expression in Cancers: Facing the Challenges. Frontiers in immunology 115 30319626
2013 Molecular pathways: human leukocyte antigen G (HLA-G). Clinical cancer research : an official journal of the American Association for Cancer Research 100 23897901
2014 HLA-G Molecules in Autoimmune Diseases and Infections. Frontiers in immunology 98 25477881
2014 HLA-G as a tolerogenic molecule in transplantation and pregnancy. Journal of immunology research 97 25143957
2014 The dual role of HLA-G in cancer. Journal of immunology research 95 24800261
2009 Non-classical transcriptional regulation of HLA-G: an update. Journal of cellular and molecular medicine 86 19508383
2007 Expression of tolerogenic HLA-G molecules in cancer prevents antitumor responses. Seminars in cancer biology 85 17881247
2014 HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction. Cellular & molecular immunology 82 24998350
2021 HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance. Frontiers in immunology 80 34777357
2014 Some basic aspects of HLA-G biology. Journal of immunology research 80 24818168
2011 The tolerogenic interplay(s) among HLA-G, myeloid APCs, and regulatory cells. Blood 80 21960588
2007 HLA-G expression in human ovarian carcinoma counteracts NK cell function. Annals of oncology : official journal of the European Society for Medical Oncology 80 17846022
2003 HLA-G and MIC expression in tumors and their role in anti-tumor immunity. Trends in immunology 80 12547505
2010 The importance of HLA-G expression in embryos, trophoblast cells, and embryonic stem cells. Cellular and molecular life sciences : CMLS 79 21080028
2001 HLA-G remains a mystery. Trends in immunology 76 11574277
2020 HLA-G: A New Immune Checkpoint in Cancer? International journal of molecular sciences 74 32630545
2001 HLA-G unique promoter region: functional implications. Immunogenetics 71 11797094
2021 HLA-G/ILTs Targeted Solid Cancer Immunotherapy: Opportunities and Challenges. Frontiers in immunology 70 34276691
2014 Immunomodulatory properties of HLA-G in infectious diseases. Journal of immunology research 70 24839609
1999 The immunotolerance role of HLA-G. Seminars in cancer biology 69 10092545
2006 Soluble HLA-G in rheumatoid arthritis. Human immunology 68 16916651
2003 HLA-G in transplantation: a relevant molecule for inhibition of graft rejection? American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 67 12492704
1997 HLA-G polymorphisms: neutral evolution or novel function? Journal of reproductive immunology 67 9430736
1999 Expression of HLA G in human tumors is not a frequent event. International journal of cancer 66 10225437
2014 Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in Reproduction. Frontiers in immunology 65 24860568
2003 HLA-G, pre-eclampsia, immunity and vascular events. Journal of reproductive immunology 65 12896824
2003 HLA-G modulates immune responses by diverse receptor interactions. Seminars in cancer biology 65 14708711
2014 New insights into HLA-G mediated tolerance. Tissue antigens 64 25132109
2006 The role of HLA-G in human pregnancy. Reproductive biology and endocrinology : RB&E 63 17118165
2020 HLA-G Neo-Expression on Tumors. Frontiers in immunology 61 32922387
2010 HLA-G and immune evasion in cancer cells. Journal of the Formosan Medical Association = Taiwan yi zhi 61 20434034
2009 HLA-G: a human pregnancy-related immunomodulator. Current opinion in pharmacology 61 19570712
2022 HLA-G: Too Much or Too Little? Role in Cancer and Autoimmune Disease. Frontiers in immunology 60 35154112
2010 Emerging topics and new perspectives on HLA-G. Cellular and molecular life sciences : CMLS 60 21080027
2000 Modulation of HLA-G expression in human thymic and amniotic epithelial cells. Human immunology 59 11137212
2010 The role of HLA-G in immunity and hematopoiesis. Cellular and molecular life sciences : CMLS 55 21116680
2005 HLA-G gene activation in tumor cells involves cis-acting epigenetic changes. International journal of cancer 55 15514928
1998 HLA-G polymorphisms and allele frequencies in Caucasians. Human immunology 55 9619769
1999 HLA-G expression in human melanoma cells: protection from NK cytolysis. Journal of reproductive immunology 53 10479054
2020 Three types of HLA-G+ extravillous trophoblasts that have distinct immune regulatory properties. Proceedings of the National Academy of Sciences of the United States of America 52 32581122
2011 HLA-G expression in human embryonic stem cells and preimplantation embryos. Journal of immunology (Baltimore, Md. : 1950) 52 21248264
2006 Structural studies on HLA-G: implications for ligand and receptor binding. Human immunology 51 17400055
2006 HLA-G expression is a fundamental prerequisite to pregnancy. Human immunology 51 17400059
2015 Biology of the immunomodulatory molecule HLA-G in human liver diseases. Journal of hepatology 50 25772038
2007 HLA-G and its role in implantation (review). Journal of assisted reproduction and genetics 49 17629722
2005 Immuno-tolerogenic functions of HLA-G: relevance in transplantation and oncology. Autoimmunity reviews 49 16214086
2020 HLA-G Genotype/Expression/Disease Association Studies: Success, Hurdles, and Perspectives. Frontiers in immunology 48 32733439
1997 Impaired spontaneous endocytosis of HLA-G. European journal of immunology 48 9368631
2008 HLA-G and inflammatory diseases. Inflammation & allergy drug targets 47 18691135
2003 HLA-G and lymphoproliferative disorders. Seminars in cancer biology 46 14708718
2011 Expression of HLA-G in patients with hepatocellular carcinoma. Hepatobiliary & pancreatic diseases international : HBPD INT 45 21459722
2010 HLA-G in organ transplantation: towards clinical applications. Cellular and molecular life sciences : CMLS 45 21103908
2009 Characterization of HLA-G expression in renal cell carcinoma. Tissue antigens 44 19531101
2007 Soluble HLA-G and control of angiogenesis. Journal of reproductive immunology 44 17467060
2021 First immunotherapeutic CAR-T cells against the immune checkpoint protein HLA-G. Journal for immunotherapy of cancer 42 33737343
2005 HLA-G*0105N null allele encodes functional HLA-G isoforms. Biology of reproduction 40 15814900
2023 HLA-G and Recurrent Pregnancy Loss. International journal of molecular sciences 39 36768880
2007 Clinical and biological significance of HLA-G expression in ovarian cancer. Seminars in cancer biology 39 17681474
2019 Intercellular transfer of HLA-G: its potential in cancer immunology. Clinical & translational immunology 38 31489189
2001 HLA-G expression by tumors. American journal of reproductive immunology (New York, N.Y. : 1989) 38 11216872
2009 HLA-G expression is up-regulated by progesterone in mesenchymal stem cells. American journal of reproductive immunology (New York, N.Y. : 1989) 37 19527229
2022 Role of HLA-G in Viral Infections. Frontiers in immunology 35 35237271
2020 Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia. EBioMedicine 35 32680723
2024 Harnessing the potential of HLA-G in cancer therapy: advances, challenges, and prospects. Journal of translational medicine 34 38310272
2011 HLA-G and pregnancy adverse outcomes. Medical hypotheses 34 21376476
2010 Interaction between HLA-G and monocyte/macrophages in human pregnancy. Journal of reproductive immunology 34 20356631
1999 HLA-G expression: immune privilege for tumour cells? Seminars in cancer biology 34 10092548
1999 The regulation of HLA class I expression: is HLA-G the odd one out? Seminars in cancer biology 34 10092551
2022 HLA-G and Other Immune Checkpoint Molecules as Targets for Novel Combined Immunotherapies. International journal of molecular sciences 33 35328349
2012 New insights into HLA-G and inflammatory diseases. Inflammation & allergy drug targets 33 22931388
2007 HLA-G expression in malignant melanoma. Seminars in cancer biology 33 17689098
2000 HLA-G in the human placenta: expression and potential functions. Biochemical Society transactions 33 10816129
1999 Immunotolerant functions of HLA-G. Cellular and molecular life sciences : CMLS 33 10228553
2021 Role of the HLA-G immune checkpoint molecule in pregnancy. Human immunology 31 33745758
2022 Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment. Frontiers in immunology 30 35185887
2005 Does 'soluble' HLA-G really exist? Another twist to the tale. Molecular human reproduction 30 16330473
2000 Analysis of the role of HLA-G in preeclampsia. Human immunology 30 11137217
2019 A role for both HLA-F and HLA-G in reproduction and during pregnancy? Human immunology 29 31558330
2020 The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis. Frontiers in immunology 28 32670296
2007 Structure, expression and function of HLA-G in renal cell carcinoma. Seminars in cancer biology 28 17707652
2000 HLA-G polymorphisms and molecule function--questions and more questions--a review. Placenta 27 10831130
2023 The Molecular Mechanisms of HLA-G Regulatory Function on Immune Cells during Early Pregnancy. Biomolecules 26 37627278
2002 HLA-G protein processing and transport to the cell surface. Cellular and molecular life sciences : CMLS 26 12440768

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