{"gene":"KIR3DL2","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2004,"finding":"KIR3DL2*001 directly and specifically binds HLA-A3 and HLA-A11 in a peptide-dependent manner; single amino acid substitutions in the nonamer peptide revealed a critical role for residue 8 in KIR3DL2 recognition, demonstrated by HLA tetramer binding to KIR3DL2 transfectants.","method":"HLA tetramer staining of KIR3DL2 transfectants; peptide analogue substitution assays","journal":"European journal of immunology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — direct binding demonstrated with tetramers on transfectants, peptide mutagenesis identifies contact residue; single lab but two orthogonal methods","pmids":["15162437"],"is_preprint":false},{"year":2007,"finding":"HLA-B27 heavy-chain homodimers (B27₂, β2m-free) bind KIR3DL2 (and KIR3DL1) independently of the sequence of the bound peptide, in contrast to HLA-B27 heterotrimers whose KIR3DL1 binding is peptide-dependent; KIR3DL2 ligation by B27₂ inhibits NK and T cell IFN-γ production.","method":"KIR transfectant binding assays with peptide-loaded vs. unloaded B27 tetramers; NK cell IFN-γ functional assays","journal":"European journal of immunology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal binding assays with multiple peptide variants and functional readout (IFN-γ inhibition), single lab, two orthogonal methods","pmids":["17407096"],"is_preprint":false},{"year":2010,"finding":"KIR3DL2 directly binds CpG oligodeoxynucleotides (ODNs) via its D0 domain, co-internalizes with CpG ODN upon NK cell stimulation, and shuttles CpG ODN to early endosomes where it encounters TLR9, thereby mediating CpG-induced IFN-γ release predominantly in KIR3DL2+ NK cells.","method":"Soluble KIR3DL2 binding assays with ODNs; flow cytometry surface down-modulation; confocal microscopy co-localization; domain-deletion mutagenesis (D0 domain); functional IFN-γ assays in KIR3DL2+ vs KIR3DL2− NK cells","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct binding with soluble receptor, domain mapping, confocal co-localization, and functional assay; multiple orthogonal methods in single rigorous study","pmids":["20147700"],"is_preprint":false},{"year":2011,"finding":"B27₂-expressing APCs stimulate the survival, proliferation, and IL-17 production of KIR3DL2+ CD4 T cells; KIR3DL2+ CD4 T cells account for the majority of IL-23R expression and produce more IL-17 in the presence of IL-23, linking HLA-B27 homodimer/KIR3DL2 interaction to Th17 expansion in spondyloarthritis.","method":"Co-culture of KIR3DL2+ CD4 T cells with B27₂-expressing APCs; intracellular cytokine staining; flow cytometry; KIR3DL2+ T cell line stimulation assays","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — functional cell co-culture assays with defined ligand (B27₂), multiple readouts (survival, proliferation, IL-17), single lab","pmids":["21248258"],"is_preprint":false},{"year":2013,"finding":"KIR3DL2 binds HLA-B27 free heavy chain (FHC) dimers more strongly than other HLA class I (including HLA-A3); B27 FHC binding induces greater KIR3DL2 phosphorylation and greater IL-2 production in KIR3DL2-CD3ε reporter T cells than HLA-A3; B27 FHC binding promotes greater survival of KIR3DL2+ CD4 T and NK cells.","method":"HLA tetramer binding to KIR3DL2-transfected cells; KIR3DL2-Fc pull-down of FHC from cell lines; KIR3DL2-CD3ε reporter T cell assays; phosphorylation assays; NK/T cell survival assays","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (pulldown, tetramer binding, reporter assay, phosphorylation, survival assay) establishing ligand hierarchy and signaling consequence in one study","pmids":["23440420"],"is_preprint":false},{"year":2013,"finding":"HLA-B*27:05 forms more cell surface B27 dimers and free heavy chain than HLA-B*27:09; cells expressing HLA-B*27:05 stimulate KIR3DL2-CD3ε reporter T cells more effectively and promote KIR3DL2+ NK cell survival more strongly than HLA-B*27:09, providing a mechanistic basis for differential AS association.","method":"In vitro B27 FHC/dimer formation assays; FACS staining with class I tetramers; KIR3DL2-CD3ε reporter T cell assays; NK cell survival assays","journal":"Rheumatology (Oxford, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional assays (reporter, survival, tetramer) comparing two alleles, single lab","pmids":["23804219"],"is_preprint":false},{"year":2014,"finding":"Engagement of KIR3DL2 by CpG ODN on malignant Sézary T cells induces receptor internalization and caspase-dependent apoptosis, correlated with dephosphorylation of constitutively activated STAT3.","method":"KIR3DL2 internalization assays; caspase inhibitor (Z-DEVD) rescue experiments; STAT3 phosphorylation western blot; flow cytometry apoptosis assays","journal":"The Journal of investigative dermatology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional engagement with ligand, caspase inhibitor rescue, and STAT3 dephosphorylation readout; single lab with multiple methods","pmids":["25007046"],"is_preprint":false},{"year":2015,"finding":"The D0 Ig-like domain of KIR3DL2 plays a central role in the stronger binding to B27 FHC dimers; mutagenesis identified key contact residues in D0, D1, and D2 domains, with modeling predicting that non-symmetrical complementary contacts of D0 and D1 with the α1, α2, and α3 domains of both B27 H chains underlie preferential binding.","method":"Site-directed mutagenesis of KIR3DL2 domains; functional binding assays on NK and reporter cells; computational modeling of B27 dimer–KIR3DL2 interface","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — mutagenesis with functional binding assays and structural modeling; single lab, two orthogonal methods","pmids":["25582852"],"is_preprint":false},{"year":2003,"finding":"KIR3DL2/p140 crosslinking on tumor-infiltrating CD8+ CTL clones did not inhibit (or activate) cytotoxicity or cytokine production triggered by anti-CD3, indicating that KIR3DL2 engagement does not produce inhibitory effects on these CTL in vitro.","method":"Antibody crosslinking of KIR3DL2 on CTL clones; 51Cr cytotoxicity assay; IFN-γ secretion assay","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct crosslinking experiments with two orthogonal functional readouts (cytotoxicity, cytokine); negative finding for inhibitory function in this CTL context; single lab","pmids":["14562047"],"is_preprint":false},{"year":2005,"finding":"KIR3DL2+ NK cells in spondyloarthritis patients display an activated phenotype and are protected from apoptosis by culture with a cell line expressing B27 homodimers (B27₂), demonstrating that KIR3DL2–B27₂ interaction promotes NK cell survival.","method":"Annexin V/7-AAD apoptosis assay; 51Cr cytotoxicity assay; co-culture of NK cells with B27₂-expressing cell line; flow cytometry activation marker staining","journal":"Arthritis and rheumatism","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — functional cell survival assay with defined ligand-expressing cell line, flow cytometry; single lab, two orthogonal methods","pmids":["16255049"],"is_preprint":false},{"year":2021,"finding":"KIR3DL2 binds CpG-DNA in a sequence-specific manner; CpG-DNA sequences common in the human genome induce inhibitory signaling in KIR3DL2+ NKL cells (reduced IFN-γ, reduced target-cell killing), whereas CpG-DNA sequences prevalent in parasitic worm genomes promote IFN-γ production and cytotoxicity, indicating KIR3DL2 differentiates self-DNA from pathogen DNA.","method":"CpG-DNA uptake assays in KIR3DL2+ NKL cells; functional IFN-γ and cytotoxicity assays with defined CpG-DNA sequences; genomic bioinformatic survey of CpG flanking sequences","journal":"PeerJ","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional assays with sequence-defined ligands and multiple readouts (DNA uptake, IFN-γ, cytotoxicity); single lab","pmids":["34760351"],"is_preprint":false},{"year":2014,"finding":"IPH4102, a humanized anti-KIR3DL2 monoclonal antibody, mediates antibody-dependent cell cytotoxicity (ADCC) and phagocytosis of KIR3DL2+ CTCL tumor cells, selectively killing primary Sézary cells ex vivo; in a mouse model of KIR3DL2+ disease, it improved survival and reduced tumor growth.","method":"In vitro ADCC and phagocytosis assays with allogeneic PBMC effectors; autologous NK-based killing assays with primary Sézary patient cells; mouse xenograft tumor model","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple in vitro and in vivo functional assays establishing mechanism of action (ADCC/phagocytosis); single lab, multiple orthogonal methods","pmids":["25361998"],"is_preprint":false}],"current_model":"KIR3DL2 is an inhibitory three-domain KIR expressed on NK cells and subsets of T cells that functions as a cell-surface receptor with at least three classes of ligands: (1) HLA-A3 and HLA-A11 heterotrimers in a peptide-dependent (position-8-critical) manner; (2) HLA-B27 β2m-free heavy chain forms (including disulfide-bonded homodimers), which bind more strongly than other HLA class I in a peptide-sequence-independent fashion, with the D0 domain and complementary D1/D2 contacts mediating preferential binding, triggering greater receptor phosphorylation and promoting lymphocyte survival; and (3) CpG oligodeoxynucleotides via its D0 domain, which are co-internalized and shuttled to early endosomes for TLR9 engagement, enabling sequence-specific discrimination of pathogen DNA from self-DNA and driving IFN-γ production in KIR3DL2+ NK cells; on malignant Sézary T cells, CpG ODN engagement additionally induces caspase-dependent apoptosis coupled to STAT3 dephosphorylation, while in spondyloarthritis the stronger KIR3DL2–B27 FHC interaction expands KIR3DL2+ Th17 cells and links HLA-B27 to IL-17 production via IL-23R signaling."},"narrative":{"mechanistic_narrative":"KIR3DL2 is a three-domain killer immunoglobulin-like receptor expressed on NK cells and T-cell subsets that operates as a ligand-discriminating cell-surface receptor coupling recognition of HLA class I and CpG-DNA to control of effector cytokine output and lymphocyte survival [PMID:15162437, PMID:20147700, PMID:23440420]. It binds HLA-A3 and HLA-A11 in a peptide-dependent manner, with peptide residue 8 critical for recognition [PMID:15162437], but engages β2m-free HLA-B27 free heavy chains and disulfide-bonded B27 homodimers more strongly and in a peptide-sequence-independent fashion, contacts mediated preferentially by the D0 domain together with complementary D1/D2 interactions across both heavy chains [PMID:23440420, PMID:25582852]. B27 free heavy-chain engagement drives greater receptor phosphorylation and signaling than HLA-A3 and promotes survival of KIR3DL2+ NK and CD4 T cells, whereas heterotrimeric class I ligation inhibits IFN-γ production [PMID:17407096, PMID:23440420]. Through its D0 domain KIR3DL2 also binds CpG oligodeoxynucleotides, co-internalizing and shuttling them to early endosomes for TLR9 engagement, and discriminates self-DNA from pathogen DNA in a sequence-specific manner to set IFN-γ and cytotoxic responses [PMID:20147700, PMID:34760351]. These activities link the receptor to disease: stronger KIR3DL2–B27 free heavy-chain interaction expands IL-23R-bearing, IL-17-producing Th17 cells in spondyloarthritis [PMID:21248258, PMID:23804219], and on malignant Sézary T cells CpG engagement triggers caspase-dependent apoptosis coupled to STAT3 dephosphorylation [PMID:25007046], making KIR3DL2 an actionable target for antibody-mediated killing of cutaneous T-cell lymphoma [PMID:25361998].","teleology":[{"year":2003,"claim":"Established that KIR3DL2 engagement does not necessarily deliver inhibitory signals in all T-cell contexts, complicating the simple inhibitory-receptor model.","evidence":"antibody crosslinking on tumor-infiltrating CD8+ CTL clones with cytotoxicity and IFN-γ readouts","pmids":["14562047"],"confidence":"Medium","gaps":["Negative finding in one CTL context only","Did not identify physiological ligand driving signaling","No biochemical signaling characterized"]},{"year":2004,"claim":"Defined the first physiological HLA ligands of KIR3DL2 and the peptide-dependence of recognition, answering what classical class I molecules the receptor reads.","evidence":"HLA tetramer staining of KIR3DL2 transfectants with peptide analogue substitution","pmids":["15162437"],"confidence":"High","gaps":["Functional consequence of A3/A11 binding not established here","Affinity relative to other ligands unknown","No structural interface defined"]},{"year":2005,"claim":"Showed that KIR3DL2–B27 homodimer interaction promotes NK cell survival in spondyloarthritis, linking the receptor to a disease-relevant ligand.","evidence":"co-culture of patient NK cells with B27₂-expressing cell line; apoptosis and activation-marker assays","pmids":["16255049"],"confidence":"Medium","gaps":["Did not resolve signaling mechanism of survival","Single patient-cell context","Causal role in disease not proven"]},{"year":2007,"claim":"Demonstrated that β2m-free HLA-B27 heavy-chain homodimers are peptide-sequence-independent ligands of KIR3DL2 that inhibit IFN-γ, distinguishing this binding mode from peptide-dependent heterotrimer recognition.","evidence":"KIR transfectant binding with loaded vs unloaded B27 tetramers; NK IFN-γ functional assays","pmids":["17407096"],"confidence":"High","gaps":["Domain basis of dimer binding not mapped","Did not quantify ligand hierarchy","Signaling downstream of inhibition uncharacterized"]},{"year":2010,"claim":"Revealed a non-HLA ligand class, showing KIR3DL2 binds CpG ODN via its D0 domain and delivers it to endosomal TLR9, defining a receptor role in innate DNA sensing.","evidence":"soluble receptor binding, D0 domain-deletion mutagenesis, confocal co-localization, IFN-γ assays","pmids":["20147700"],"confidence":"High","gaps":["Sequence selectivity of CpG binding not defined here","Physiological source of CpG ligand unaddressed","Relationship to HLA-binding function unclear"]},{"year":2011,"claim":"Connected the KIR3DL2–B27 dimer axis to Th17 biology, showing it drives IL-17 production and IL-23R expression in CD4 T cells relevant to spondyloarthritis.","evidence":"co-culture of KIR3DL2+ CD4 T cells with B27₂-APCs; intracellular cytokine staining","pmids":["21248258"],"confidence":"Medium","gaps":["Signaling pathway linking receptor to IL-17 not resolved","In vitro system only","Causal contribution to clinical disease not established"]},{"year":2013,"claim":"Quantified the ligand hierarchy and signaling consequences, establishing that B27 free heavy chain binds more strongly than HLA-A3 and drives greater phosphorylation, IL-2 output, and lymphocyte survival.","evidence":"tetramer binding, KIR3DL2-Fc pulldown, KIR3DL2-CD3ε reporter assays, phosphorylation and survival assays","pmids":["23440420"],"confidence":"High","gaps":["Endogenous signaling adaptors not identified","Structural interface predicted not solved","Link between phosphorylation and survival mechanistically incomplete"]},{"year":2013,"claim":"Provided a molecular basis for differential disease association by linking allele-specific B27 dimer/FHC formation to differential KIR3DL2 stimulation.","evidence":"comparison of HLA-B*27:05 vs B*27:09 dimer formation, reporter and NK survival assays","pmids":["23804219"],"confidence":"Medium","gaps":["Direct genetic disease causation not tested","Mechanism of differential dimer formation not the focus","Single in vitro system"]},{"year":2014,"claim":"Mapped the apoptotic consequence of CpG engagement in malignant cells, showing KIR3DL2 ligation triggers caspase-dependent death and STAT3 dephosphorylation in Sézary cells.","evidence":"internalization assays, caspase-inhibitor rescue, STAT3 phosphorylation western blot, apoptosis assays","pmids":["25007046"],"confidence":"Medium","gaps":["Signaling link between receptor and STAT3 not defined","Restricted to Sézary cell context","Endogenous CpG trigger in vivo unknown"]},{"year":2014,"claim":"Validated KIR3DL2 as a therapeutic target, demonstrating that an anti-KIR3DL2 antibody mediates ADCC/phagocytosis and tumor control in CTCL models.","evidence":"in vitro ADCC/phagocytosis with primary Sézary cells; mouse xenograft model","pmids":["25361998"],"confidence":"Medium","gaps":["Single antibody/agent tested","Mechanism of selective tumor expression not addressed","Clinical efficacy not established here"]},{"year":2015,"claim":"Resolved the structural basis of preferential B27 dimer binding, identifying D0 as central and defining complementary D0/D1 contacts across both heavy chains.","evidence":"site-directed mutagenesis of receptor domains, functional binding assays, computational interface modeling","pmids":["25582852"],"confidence":"Medium","gaps":["Model not validated by experimental structure","Contact residues inferred from modeling","Single lab"]},{"year":2021,"claim":"Established sequence-specific self/non-self DNA discrimination, showing genome-common CpG drives inhibition while parasite-prevalent CpG drives activation.","evidence":"CpG-DNA uptake, IFN-γ and cytotoxicity assays with defined sequences, genomic bioinformatic survey","pmids":["34760351"],"confidence":"Medium","gaps":["Molecular basis of sequence discrimination not solved","NKL cell line model only","In vivo relevance to anti-parasite immunity untested"]},{"year":null,"claim":"How KIR3DL2 integrates opposing inhibitory versus activating outcomes across its HLA and CpG ligands at the level of cytoplasmic signaling adaptors remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No experimental structure of any ligand complex","Cytoplasmic signaling adaptors and ITIM/ITAM usage not directly characterized in corpus","Mechanism switching between inhibition and activation undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0001618","term_label":"virus receptor activity","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[2,10]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[1,4]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,2,4]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,2,4]}],"complexes":[],"partners":["HLA-B27","HLA-A3","HLA-A11","TLR9"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P43630","full_name":"Killer cell immunoglobulin-like receptor 3DL2","aliases":["CD158 antigen-like family member K","Natural killer-associated transcript 4","NKAT-4","p70 natural killer cell receptor clone CL-5","p70 NK receptor CL-5"],"length_aa":455,"mass_kda":50.2,"function":"Receptor on natural killer (NK) cells and T cells for MHC class I molecules (PubMed:24018270, PubMed:28636952). Upon binding of peptide-free HLA-F open conformer, negatively regulates NK and T cell effector functions (PubMed:24018270). Acts as a receptor on astrocytes for HLA-F. Through interaction with HLA-F, may protect motor neurons from astrocyte-induced toxicity (PubMed:26928464)","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/P43630/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KIR3DL2","classification":"Not Classified","n_dependent_lines":21,"n_total_lines":1208,"dependency_fraction":0.0173841059602649},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KIR3DL2","total_profiled":1310},"omim":[{"mim_id":"604947","title":"KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTOR, THREE DOMAINS, LONG CYTOPLASMIC TAIL, 2; KIR3DL2","url":"https://www.omim.org/entry/604947"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":1.8}],"url":"https://www.proteinatlas.org/search/KIR3DL2"},"hgnc":{"alias_symbol":["cl-5","nkat4","nkat4a","nkat4b","CD158K"],"prev_symbol":[]},"alphafold":{"accession":"P43630","domains":[{"cath_id":"2.60.40.10","chopping":"29-117","consensus_level":"high","plddt":80.6217,"start":29,"end":117},{"cath_id":"2.60.40.10","chopping":"122-217","consensus_level":"high","plddt":93.6421,"start":122,"end":217},{"cath_id":"2.60.40.10","chopping":"224-315","consensus_level":"high","plddt":92.0772,"start":224,"end":315}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P43630","model_url":"https://alphafold.ebi.ac.uk/files/AF-P43630-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P43630-F1-predicted_aligned_error_v6.png","plddt_mean":74.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIR3DL2","jax_strain_url":"https://www.jax.org/strain/search?query=KIR3DL2"},"sequence":{"accession":"P43630","fasta_url":"https://rest.uniprot.org/uniprotkb/P43630.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P43630/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P43630"}},"corpus_meta":[{"pmid":"15162437","id":"PMC_15162437","title":"Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is peptide-specific.","date":"2004","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/15162437","citation_count":262,"is_preprint":false},{"pmid":"21248258","id":"PMC_21248258","title":"Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis.","date":"2011","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/21248258","citation_count":229,"is_preprint":false},{"pmid":"19858347","id":"PMC_19858347","title":"KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C.","date":"2009","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/19858347","citation_count":201,"is_preprint":false},{"pmid":"16255049","id":"PMC_16255049","title":"Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis.","date":"2005","source":"Arthritis and rheumatism","url":"https://pubmed.ncbi.nlm.nih.gov/16255049","citation_count":157,"is_preprint":false},{"pmid":"31253572","id":"PMC_31253572","title":"IPH4102, a first-in-class anti-KIR3DL2 monoclonal antibody, in patients with relapsed or refractory cutaneous T-cell lymphoma: an international, first-in-human, open-label, phase 1 trial.","date":"2019","source":"The Lancet. 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chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19842663","citation_count":13,"is_preprint":false},{"pmid":"17661911","id":"PMC_17661911","title":"KIR3DL2: diversity in a hematopoietic stem cell transplant population.","date":"2007","source":"Tissue antigens","url":"https://pubmed.ncbi.nlm.nih.gov/17661911","citation_count":9,"is_preprint":false},{"pmid":"35687761","id":"PMC_35687761","title":"KIR3DL2 contributes to the typing of acute adult T-cell leukemia and is a potential therapeutic target.","date":"2022","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/35687761","citation_count":8,"is_preprint":false},{"pmid":"25582852","id":"PMC_25582852","title":"The D0 Ig-like domain plays a central role in the stronger binding of KIR3DL2 to B27 free H chain dimers.","date":"2015","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/25582852","citation_count":8,"is_preprint":false},{"pmid":"25033772","id":"PMC_25033772","title":"Two new cases of KIR3DP1, KIR2DL4-negative genotypes, one of which is also lacking KIR3DL2.","date":"2014","source":"Archivum immunologiae et therapiae experimentalis","url":"https://pubmed.ncbi.nlm.nih.gov/25033772","citation_count":7,"is_preprint":false},{"pmid":"38588023","id":"PMC_38588023","title":"Structural Phase Transition in 0D (3,5-DMP)2Bi1-SbCl5 Metal Halides: Expression of the Lone Pair Effect and Polyhedral Distortion.","date":"2024","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38588023","citation_count":7,"is_preprint":false},{"pmid":"32219695","id":"PMC_32219695","title":"Potential antipsychotic action of the selective agonist of adenosine A1 receptors, 5'-Cl-5'-deoxy-ENBA, in amphetamine and MK-801 rat models.","date":"2020","source":"Pharmacological reports : PR","url":"https://pubmed.ncbi.nlm.nih.gov/32219695","citation_count":7,"is_preprint":false},{"pmid":"34760351","id":"PMC_34760351","title":"Abundant CpG-sequences in human genomes inhibit KIR3DL2-expressing NK cells.","date":"2021","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/34760351","citation_count":6,"is_preprint":false},{"pmid":"25407699","id":"PMC_25407699","title":"Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma with KIR3DL2 and NKp46 expression in a human immunodeficiency virus carrier.","date":"2014","source":"Journal of cutaneous pathology","url":"https://pubmed.ncbi.nlm.nih.gov/25407699","citation_count":6,"is_preprint":false},{"pmid":"32642289","id":"PMC_32642289","title":"Novel genetic variants of KIR3DL2 and PVR involved in immunoregulatory interactions are associated with non-small cell lung cancer survival.","date":"2020","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/32642289","citation_count":4,"is_preprint":false},{"pmid":"34971634","id":"PMC_34971634","title":"Fine definition of the epitopes on the human gp91phox/NOX2 for the monoclonal antibodies CL-5 and 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peptide-dependent manner; single amino acid substitutions in the nonamer peptide revealed a critical role for residue 8 in KIR3DL2 recognition, demonstrated by HLA tetramer binding to KIR3DL2 transfectants.\",\n      \"method\": \"HLA tetramer staining of KIR3DL2 transfectants; peptide analogue substitution assays\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — direct binding demonstrated with tetramers on transfectants, peptide mutagenesis identifies contact residue; single lab but two orthogonal methods\",\n      \"pmids\": [\"15162437\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"HLA-B27 heavy-chain homodimers (B27₂, β2m-free) bind KIR3DL2 (and KIR3DL1) independently of the sequence of the bound peptide, in contrast to HLA-B27 heterotrimers whose KIR3DL1 binding is peptide-dependent; KIR3DL2 ligation by B27₂ inhibits NK and T cell IFN-γ production.\",\n      \"method\": \"KIR transfectant binding assays with peptide-loaded vs. unloaded B27 tetramers; NK cell IFN-γ functional assays\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding assays with multiple peptide variants and functional readout (IFN-γ inhibition), single lab, two orthogonal methods\",\n      \"pmids\": [\"17407096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"KIR3DL2 directly binds CpG oligodeoxynucleotides (ODNs) via its D0 domain, co-internalizes with CpG ODN upon NK cell stimulation, and shuttles CpG ODN to early endosomes where it encounters TLR9, thereby mediating CpG-induced IFN-γ release predominantly in KIR3DL2+ NK cells.\",\n      \"method\": \"Soluble KIR3DL2 binding assays with ODNs; flow cytometry surface down-modulation; confocal microscopy co-localization; domain-deletion mutagenesis (D0 domain); functional IFN-γ assays in KIR3DL2+ vs KIR3DL2− NK cells\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct binding with soluble receptor, domain mapping, confocal co-localization, and functional assay; multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"20147700\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"B27₂-expressing APCs stimulate the survival, proliferation, and IL-17 production of KIR3DL2+ CD4 T cells; KIR3DL2+ CD4 T cells account for the majority of IL-23R expression and produce more IL-17 in the presence of IL-23, linking HLA-B27 homodimer/KIR3DL2 interaction to Th17 expansion in spondyloarthritis.\",\n      \"method\": \"Co-culture of KIR3DL2+ CD4 T cells with B27₂-expressing APCs; intracellular cytokine staining; flow cytometry; KIR3DL2+ T cell line stimulation assays\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — functional cell co-culture assays with defined ligand (B27₂), multiple readouts (survival, proliferation, IL-17), single lab\",\n      \"pmids\": [\"21248258\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIR3DL2 binds HLA-B27 free heavy chain (FHC) dimers more strongly than other HLA class I (including HLA-A3); B27 FHC binding induces greater KIR3DL2 phosphorylation and greater IL-2 production in KIR3DL2-CD3ε reporter T cells than HLA-A3; B27 FHC binding promotes greater survival of KIR3DL2+ CD4 T and NK cells.\",\n      \"method\": \"HLA tetramer binding to KIR3DL2-transfected cells; KIR3DL2-Fc pull-down of FHC from cell lines; KIR3DL2-CD3ε reporter T cell assays; phosphorylation assays; NK/T cell survival assays\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (pulldown, tetramer binding, reporter assay, phosphorylation, survival assay) establishing ligand hierarchy and signaling consequence in one study\",\n      \"pmids\": [\"23440420\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"HLA-B*27:05 forms more cell surface B27 dimers and free heavy chain than HLA-B*27:09; cells expressing HLA-B*27:05 stimulate KIR3DL2-CD3ε reporter T cells more effectively and promote KIR3DL2+ NK cell survival more strongly than HLA-B*27:09, providing a mechanistic basis for differential AS association.\",\n      \"method\": \"In vitro B27 FHC/dimer formation assays; FACS staining with class I tetramers; KIR3DL2-CD3ε reporter T cell assays; NK cell survival assays\",\n      \"journal\": \"Rheumatology (Oxford, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional assays (reporter, survival, tetramer) comparing two alleles, single lab\",\n      \"pmids\": [\"23804219\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Engagement of KIR3DL2 by CpG ODN on malignant Sézary T cells induces receptor internalization and caspase-dependent apoptosis, correlated with dephosphorylation of constitutively activated STAT3.\",\n      \"method\": \"KIR3DL2 internalization assays; caspase inhibitor (Z-DEVD) rescue experiments; STAT3 phosphorylation western blot; flow cytometry apoptosis assays\",\n      \"journal\": \"The Journal of investigative dermatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional engagement with ligand, caspase inhibitor rescue, and STAT3 dephosphorylation readout; single lab with multiple methods\",\n      \"pmids\": [\"25007046\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The D0 Ig-like domain of KIR3DL2 plays a central role in the stronger binding to B27 FHC dimers; mutagenesis identified key contact residues in D0, D1, and D2 domains, with modeling predicting that non-symmetrical complementary contacts of D0 and D1 with the α1, α2, and α3 domains of both B27 H chains underlie preferential binding.\",\n      \"method\": \"Site-directed mutagenesis of KIR3DL2 domains; functional binding assays on NK and reporter cells; computational modeling of B27 dimer–KIR3DL2 interface\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — mutagenesis with functional binding assays and structural modeling; single lab, two orthogonal methods\",\n      \"pmids\": [\"25582852\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"KIR3DL2/p140 crosslinking on tumor-infiltrating CD8+ CTL clones did not inhibit (or activate) cytotoxicity or cytokine production triggered by anti-CD3, indicating that KIR3DL2 engagement does not produce inhibitory effects on these CTL in vitro.\",\n      \"method\": \"Antibody crosslinking of KIR3DL2 on CTL clones; 51Cr cytotoxicity assay; IFN-γ secretion assay\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct crosslinking experiments with two orthogonal functional readouts (cytotoxicity, cytokine); negative finding for inhibitory function in this CTL context; single lab\",\n      \"pmids\": [\"14562047\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"KIR3DL2+ NK cells in spondyloarthritis patients display an activated phenotype and are protected from apoptosis by culture with a cell line expressing B27 homodimers (B27₂), demonstrating that KIR3DL2–B27₂ interaction promotes NK cell survival.\",\n      \"method\": \"Annexin V/7-AAD apoptosis assay; 51Cr cytotoxicity assay; co-culture of NK cells with B27₂-expressing cell line; flow cytometry activation marker staining\",\n      \"journal\": \"Arthritis and rheumatism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — functional cell survival assay with defined ligand-expressing cell line, flow cytometry; single lab, two orthogonal methods\",\n      \"pmids\": [\"16255049\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KIR3DL2 binds CpG-DNA in a sequence-specific manner; CpG-DNA sequences common in the human genome induce inhibitory signaling in KIR3DL2+ NKL cells (reduced IFN-γ, reduced target-cell killing), whereas CpG-DNA sequences prevalent in parasitic worm genomes promote IFN-γ production and cytotoxicity, indicating KIR3DL2 differentiates self-DNA from pathogen DNA.\",\n      \"method\": \"CpG-DNA uptake assays in KIR3DL2+ NKL cells; functional IFN-γ and cytotoxicity assays with defined CpG-DNA sequences; genomic bioinformatic survey of CpG flanking sequences\",\n      \"journal\": \"PeerJ\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional assays with sequence-defined ligands and multiple readouts (DNA uptake, IFN-γ, cytotoxicity); single lab\",\n      \"pmids\": [\"34760351\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"IPH4102, a humanized anti-KIR3DL2 monoclonal antibody, mediates antibody-dependent cell cytotoxicity (ADCC) and phagocytosis of KIR3DL2+ CTCL tumor cells, selectively killing primary Sézary cells ex vivo; in a mouse model of KIR3DL2+ disease, it improved survival and reduced tumor growth.\",\n      \"method\": \"In vitro ADCC and phagocytosis assays with allogeneic PBMC effectors; autologous NK-based killing assays with primary Sézary patient cells; mouse xenograft tumor model\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple in vitro and in vivo functional assays establishing mechanism of action (ADCC/phagocytosis); single lab, multiple orthogonal methods\",\n      \"pmids\": [\"25361998\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KIR3DL2 is an inhibitory three-domain KIR expressed on NK cells and subsets of T cells that functions as a cell-surface receptor with at least three classes of ligands: (1) HLA-A3 and HLA-A11 heterotrimers in a peptide-dependent (position-8-critical) manner; (2) HLA-B27 β2m-free heavy chain forms (including disulfide-bonded homodimers), which bind more strongly than other HLA class I in a peptide-sequence-independent fashion, with the D0 domain and complementary D1/D2 contacts mediating preferential binding, triggering greater receptor phosphorylation and promoting lymphocyte survival; and (3) CpG oligodeoxynucleotides via its D0 domain, which are co-internalized and shuttled to early endosomes for TLR9 engagement, enabling sequence-specific discrimination of pathogen DNA from self-DNA and driving IFN-γ production in KIR3DL2+ NK cells; on malignant Sézary T cells, CpG ODN engagement additionally induces caspase-dependent apoptosis coupled to STAT3 dephosphorylation, while in spondyloarthritis the stronger KIR3DL2–B27 FHC interaction expands KIR3DL2+ Th17 cells and links HLA-B27 to IL-17 production via IL-23R signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIR3DL2 is a three-domain killer immunoglobulin-like receptor expressed on NK cells and T-cell subsets that operates as a ligand-discriminating cell-surface receptor coupling recognition of HLA class I and CpG-DNA to control of effector cytokine output and lymphocyte survival [#0, #2, #4]. It binds HLA-A3 and HLA-A11 in a peptide-dependent manner, with peptide residue 8 critical for recognition [#0], but engages \\u03b22m-free HLA-B27 free heavy chains and disulfide-bonded B27 homodimers more strongly and in a peptide-sequence-independent fashion, contacts mediated preferentially by the D0 domain together with complementary D1/D2 interactions across both heavy chains [#4, #7]. B27 free heavy-chain engagement drives greater receptor phosphorylation and signaling than HLA-A3 and promotes survival of KIR3DL2+ NK and CD4 T cells, whereas heterotrimeric class I ligation inhibits IFN-\\u03b3 production [#1, #4]. Through its D0 domain KIR3DL2 also binds CpG oligodeoxynucleotides, co-internalizing and shuttling them to early endosomes for TLR9 engagement, and discriminates self-DNA from pathogen DNA in a sequence-specific manner to set IFN-\\u03b3 and cytotoxic responses [#2, #10]. These activities link the receptor to disease: stronger KIR3DL2\\u2013B27 free heavy-chain interaction expands IL-23R-bearing, IL-17-producing Th17 cells in spondyloarthritis [#3, #5], and on malignant S\\u00e9zary T cells CpG engagement triggers caspase-dependent apoptosis coupled to STAT3 dephosphorylation [#6], making KIR3DL2 an actionable target for antibody-mediated killing of cutaneous T-cell lymphoma [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established that KIR3DL2 engagement does not necessarily deliver inhibitory signals in all T-cell contexts, complicating the simple inhibitory-receptor model.\",\n      \"evidence\": \"antibody crosslinking on tumor-infiltrating CD8+ CTL clones with cytotoxicity and IFN-\\u03b3 readouts\",\n      \"pmids\": [\"14562047\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Negative finding in one CTL context only\", \"Did not identify physiological ligand driving signaling\", \"No biochemical signaling characterized\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Defined the first physiological HLA ligands of KIR3DL2 and the peptide-dependence of recognition, answering what classical class I molecules the receptor reads.\",\n      \"evidence\": \"HLA tetramer staining of KIR3DL2 transfectants with peptide analogue substitution\",\n      \"pmids\": [\"15162437\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of A3/A11 binding not established here\", \"Affinity relative to other ligands unknown\", \"No structural interface defined\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Showed that KIR3DL2\\u2013B27 homodimer interaction promotes NK cell survival in spondyloarthritis, linking the receptor to a disease-relevant ligand.\",\n      \"evidence\": \"co-culture of patient NK cells with B27\\u2082-expressing cell line; apoptosis and activation-marker assays\",\n      \"pmids\": [\"16255049\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not resolve signaling mechanism of survival\", \"Single patient-cell context\", \"Causal role in disease not proven\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstrated that \\u03b22m-free HLA-B27 heavy-chain homodimers are peptide-sequence-independent ligands of KIR3DL2 that inhibit IFN-\\u03b3, distinguishing this binding mode from peptide-dependent heterotrimer recognition.\",\n      \"evidence\": \"KIR transfectant binding with loaded vs unloaded B27 tetramers; NK IFN-\\u03b3 functional assays\",\n      \"pmids\": [\"17407096\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Domain basis of dimer binding not mapped\", \"Did not quantify ligand hierarchy\", \"Signaling downstream of inhibition uncharacterized\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Revealed a non-HLA ligand class, showing KIR3DL2 binds CpG ODN via its D0 domain and delivers it to endosomal TLR9, defining a receptor role in innate DNA sensing.\",\n      \"evidence\": \"soluble receptor binding, D0 domain-deletion mutagenesis, confocal co-localization, IFN-\\u03b3 assays\",\n      \"pmids\": [\"20147700\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Sequence selectivity of CpG binding not defined here\", \"Physiological source of CpG ligand unaddressed\", \"Relationship to HLA-binding function unclear\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Connected the KIR3DL2\\u2013B27 dimer axis to Th17 biology, showing it drives IL-17 production and IL-23R expression in CD4 T cells relevant to spondyloarthritis.\",\n      \"evidence\": \"co-culture of KIR3DL2+ CD4 T cells with B27\\u2082-APCs; intracellular cytokine staining\",\n      \"pmids\": [\"21248258\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signaling pathway linking receptor to IL-17 not resolved\", \"In vitro system only\", \"Causal contribution to clinical disease not established\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Quantified the ligand hierarchy and signaling consequences, establishing that B27 free heavy chain binds more strongly than HLA-A3 and drives greater phosphorylation, IL-2 output, and lymphocyte survival.\",\n      \"evidence\": \"tetramer binding, KIR3DL2-Fc pulldown, KIR3DL2-CD3\\u03b5 reporter assays, phosphorylation and survival assays\",\n      \"pmids\": [\"23440420\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Endogenous signaling adaptors not identified\", \"Structural interface predicted not solved\", \"Link between phosphorylation and survival mechanistically incomplete\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Provided a molecular basis for differential disease association by linking allele-specific B27 dimer/FHC formation to differential KIR3DL2 stimulation.\",\n      \"evidence\": \"comparison of HLA-B*27:05 vs B*27:09 dimer formation, reporter and NK survival assays\",\n      \"pmids\": [\"23804219\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct genetic disease causation not tested\", \"Mechanism of differential dimer formation not the focus\", \"Single in vitro system\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Mapped the apoptotic consequence of CpG engagement in malignant cells, showing KIR3DL2 ligation triggers caspase-dependent death and STAT3 dephosphorylation in S\\u00e9zary cells.\",\n      \"evidence\": \"internalization assays, caspase-inhibitor rescue, STAT3 phosphorylation western blot, apoptosis assays\",\n      \"pmids\": [\"25007046\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signaling link between receptor and STAT3 not defined\", \"Restricted to S\\u00e9zary cell context\", \"Endogenous CpG trigger in vivo unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Validated KIR3DL2 as a therapeutic target, demonstrating that an anti-KIR3DL2 antibody mediates ADCC/phagocytosis and tumor control in CTCL models.\",\n      \"evidence\": \"in vitro ADCC/phagocytosis with primary S\\u00e9zary cells; mouse xenograft model\",\n      \"pmids\": [\"25361998\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single antibody/agent tested\", \"Mechanism of selective tumor expression not addressed\", \"Clinical efficacy not established here\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Resolved the structural basis of preferential B27 dimer binding, identifying D0 as central and defining complementary D0/D1 contacts across both heavy chains.\",\n      \"evidence\": \"site-directed mutagenesis of receptor domains, functional binding assays, computational interface modeling\",\n      \"pmids\": [\"25582852\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Model not validated by experimental structure\", \"Contact residues inferred from modeling\", \"Single lab\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Established sequence-specific self/non-self DNA discrimination, showing genome-common CpG drives inhibition while parasite-prevalent CpG drives activation.\",\n      \"evidence\": \"CpG-DNA uptake, IFN-\\u03b3 and cytotoxicity assays with defined sequences, genomic bioinformatic survey\",\n      \"pmids\": [\"34760351\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of sequence discrimination not solved\", \"NKL cell line model only\", \"In vivo relevance to anti-parasite immunity untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KIR3DL2 integrates opposing inhibitory versus activating outcomes across its HLA and CpG ligands at the level of cytoplasmic signaling adaptors remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No experimental structure of any ligand complex\", \"Cytoplasmic signaling adaptors and ITIM/ITAM usage not directly characterized in corpus\", \"Mechanism switching between inhibition and activation undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0001618\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [2, 10]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 2, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"HLA-B27\", \"HLA-A3\", \"HLA-A11\", \"TLR9\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}