{"id":"ca7865c7-0c79-5b78-b61d-d5185bd772bc","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-gcn2-gvhd","predicate":"not_required_for_ido_response","statement":"Donor mouse T cells lacking GCN2 still responded to IDO-mediated suppression in graft-versus-host disease experiments.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"0b696586-1522-5518-8efe-909e64bcfab2","mechanism_event_label":"In a transplant model, IDO suppression also persisted without GCN2.","subject":{"id":"3876a24a-f6fe-5900-8ce2-22525a4faacb","slug":"mouse-eif2ak4","display_name":"Mouse GCN2 / Eif2ak4","entity_type_key":"protein"},"object":{"id":"e3a78d01-11ad-5bbd-8beb-7a07979f58eb","slug":"mouse-trp-limited-t-cell-proliferation","display_name":"Mouse T-cell proliferation under tryptophan limitation or IDO exposure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0b696586-1522-5518-8efe-909e64bcfab2","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-gcn2-gvhd-event","event_type":"observed_relationship","label":"In a transplant model, IDO suppression also persisted without GCN2.","description":"Donor mouse T cells lacking GCN2 still responded to IDO-mediated suppression in graft-versus-host disease experiments.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3876a24a-f6fe-5900-8ce2-22525a4faacb","slug":"mouse-eif2ak4","display_name":"Mouse GCN2 / Eif2ak4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e3a78d01-11ad-5bbd-8beb-7a07979f58eb","slug":"mouse-trp-limited-t-cell-proliferation","display_name":"Mouse T-cell proliferation under tryptophan limitation or IDO exposure","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"769339cb-213b-559e-acc0-07ed00368b94","slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse allogeneic transplantation and donor T-cell genetics.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The authors favor metabolite-mediated suppression; it does not prove which single metabolite explains all models.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"In a transplant model, IDO suppression also persisted without GCN2.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Inducing the tryptophan catabolic pathway, indoleamine 2,3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19828695/ · DOI 10.1182/blood-2009-06-227587","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"27e40908-61da-5503-bc87-6e0e1238da27","evidence_kind":"source_excerpt","locator":"Lines 394-400","start_line":394,"end_line":400,"excerpt":"## tryptophan-gcn2-gvhd\nIn a transplant model, IDO suppression also persisted without GCN2.\nDonor mouse T cells lacking GCN2 still responded to IDO-mediated suppression in graft-versus-host disease experiments.\nModel: Mouse allogeneic transplantation and donor T-cell genetics.\nLimitations: The authors favor metabolite-mediated suppression; it does not prove which single metabolite explains all models.\nEvidence access: Primary abstract\nInducing the tryptophan catabolic pathway, indoleamine 2,3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19828695/ · DOI 10.1182/blood-2009-06-227587","model_system":"Mouse allogeneic transplantation and donor T-cell genetics.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73f9d3e7-fdc9-5418-8f3c-f4ef145f6efa","stable_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"7dfd20063b91900cb5c6ad675e3e675b7e25ef0fb8304eabac6f263cc5518284","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"f7e65909-03f5-5feb-adc2-0a692f35089a","title":"Is GCN2 required for T-cell arrest during tryptophan limitation?","kind":"contradiction","status":"open","why":"The 2005 IDO-dendritic-cell study found GCN2-deficient T cells resistant to suppression; the 2016 genetic study found GCN2-deficient CD8 cells still unable to proliferate under amino-acid limitation and explicitly challenged the earlier model.","resolution":"Keep the necessity question open across settings. T-cell subsets, genetic backgrounds, dendritic-cell signals and metabolite exposure differ. GCN2-dependent CHOP induction can be separated from proliferative arrest. The GVHD result adds a distinct model in which GCN2 was not required; it does not settle every context.","created_at":"2026-09-19 06:25:16","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/f7e65909-03f5-5feb-adc2-0a692f35089a","sides":[{"conflict_id":"f7e65909-03f5-5feb-adc2-0a692f35089a","ordinal":0,"label":"GCN2 necessary in IDO-dendritic-cell study","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","start_line":370,"end_line":376,"quote":"## tryptophan-gcn2-required\nOne study found this nutrient-stress sensor necessary for suppression.\nGCN2-deficient mouse T cells resisted suppression and anergy imposed by IDO-expressing dendritic cells in the 2005 study.\nModel: Mouse Gcn2 knockout, IDO-positive plasmacytoid/tumor-draining dendritic-cell experiments.\nLimitations: A later genetic study reports arrest without GCN2; necessity is not universal across the available evidence.\nEvidence access: Primary abstract\nGCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15894280/ · DOI 10.1016/j.immuni.2005.03.013","source_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","source_title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","claim_ids":["3821b2c1-7358-555c-bf94-58ca82976e54"]},{"conflict_id":"f7e65909-03f5-5feb-adc2-0a692f35089a","ordinal":1,"label":"Arrest persists without GCN2 in defined limitation","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","start_line":378,"end_line":384,"quote":"## tryptophan-gcn2-not-required\nAnother study found the division block persisted without that sensor.\nGCN2-deficient mouse CD8 T cells still failed to proliferate under limiting tryptophan, arginine, leucine, lysine or asparagine in the 2016 study.\nModel: Gcn2-deficient mice crossed to TCR-transgenic backgrounds; defined amino-acid limitation.\nLimitations: Not identical to every IDO-dendritic-cell preparation; the authors explicitly challenge the earlier necessity model.\nEvidence access: Primary abstract\nStress Kinase GCN2 Controls the Proliferative Fitness and Trafficking of Cytotoxic T Cells Independent of Environmental Amino Acid Sensing. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27880901/ · DOI 10.1016/j.celrep.2016.10.079","source_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","source_title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","claim_ids":["f32a34a2-ecaf-5908-8ca3-601353af879d"]},{"conflict_id":"f7e65909-03f5-5feb-adc2-0a692f35089a","ordinal":2,"label":"GCN2-independent IDO response in GVHD","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","start_line":394,"end_line":400,"quote":"## tryptophan-gcn2-gvhd\nIn a transplant model, IDO suppression also persisted without GCN2.\nDonor mouse T cells lacking GCN2 still responded to IDO-mediated suppression in graft-versus-host disease experiments.\nModel: Mouse allogeneic transplantation and donor T-cell genetics.\nLimitations: The authors favor metabolite-mediated suppression; it does not prove which single metabolite explains all models.\nEvidence access: Primary abstract\nInducing the tryptophan catabolic pathway, indoleamine 2,3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19828695/ · DOI 10.1182/blood-2009-06-227587","source_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","source_title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","claim_ids":["ca7865c7-0c79-5b78-b61d-d5185bd772bc"]}]}],"corrections":[],"research":null}