{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T19:37:40Z","timestamp":1777750660243,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,27]]},"group-title":"Cell Biology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["2023\/05075-0"],"award-info":[{"award-number":["2023\/05075-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["2R01 AG056058"],"award-info":[{"award-number":["2R01 AG056058"]}]},{"name":"NSF","award":["1625770"],"award-info":[{"award-number":["1625770"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,27]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>Protein aggregation, impaired degradation, and immune activation are central hallmarks of neurodegenerative diseases, yet how these processes are coordinated remains unclear. Here, we identify Immune-Protein Degradation Bodies (I-PDBs), a previously unrecognized class of BAG2-driven, phase-separated organelles that integrate protein quality control with adaptive immunity. IFN\u03b3 induce I-PDB formation at the endoplasmic reticulum (ER), where they concentrate immunoproteasome components, MHC-I peptide-loading machinery, and ER-associated chaperones. I-PDBs redirect proteostatic cargo from centrosomal aggregation pathways to spatially restricted degradation sites optimized for antigenic peptide generation, coupling selective substrate clearance to CD8\u207a T cell engagement. Using a cellular model of aggregation-prone tau, we show that I-PDBs capture pathological tau fibrils at ER\u2013microtubule interfaces and process them into potentially antigenic peptides, thus reducing the load of aggregation-prone tau peptides. We term this mechanism the Proteostasis-Associated Immune Relay (PAIR), establishing I-PDBs as critical hubs linking proteostasis to immune surveillance with broad implications for disease.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"719751v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>IFN\u03b3 drives BAG2-dependent Immune-Protein Degradation Bodies (I-PDBs)<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>I-PDBs assemble at the endoplasmic reticulum and are enriched in immunoproteasome and MHC-I machinery<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>I-PDBs shunt misfolded proteins, including pathological tau, away from aggresomes<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>I-PDBs couple proteostasis to antigen presentation, enhancing CD8\u207a T cell recognition<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>The Proteostasis-Associated Immune Relay (PAIR) defines a pathway linking proteostasis to adaptive immunity<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.24.719751","type":"posted-content","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:10:29Z","timestamp":1777281029000},"source":"Crossref","is-referenced-by-count":0,"title":["BAG2 Condensates Couple Proteostasis to CD8\n                  <sup>+<\/sup>\n                  T Cell Surveillance"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2012-3169","authenticated-orcid":false,"given":"Maria C.","family":"Almeida","sequence":"first","affiliation":[{"name":"Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA"},{"name":"Center for Natural and Human Sciences (CCNH), Federal University of ABC, S\u00e3o Bernardo do Campo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4007-7710","authenticated-orcid":false,"given":"Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0599-5030","authenticated-orcid":false,"given":"Andrew P.","family":"Longhini","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1162-8798","authenticated-orcid":false,"given":"Samuel","family":"Lobo","sequence":"additional","affiliation":[{"name":"Center for Mathematics, Computing and Cognition (CMCC), Federal University of ABC, S\u00e3o Bernardo do Campo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5918-4081","authenticated-orcid":false,"given":"Carolina M.","family":"Camargo","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1641-9572","authenticated-orcid":false,"given":"Eric D.","family":"Tinkle","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0937-4022","authenticated-orcid":false,"given":"Mookwang","family":"Kwon","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4014-0419","authenticated-orcid":false,"given":"Guilherme Z.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Center for Natural and Human Sciences (CCNH), Federal University of ABC, S\u00e3o Bernardo do Campo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0078-657X","authenticated-orcid":false,"given":"Isabel O.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Center for Natural and Human Sciences (CCNH), Federal University of ABC, S\u00e3o Bernardo do Campo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4604-9945","authenticated-orcid":false,"given":"Cesar A.J.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Center for Natural and Human Sciences (CCNH), Federal University of ABC, S\u00e3o Bernardo do Campo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1632-4267","authenticated-orcid":false,"given":"Fernando A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Center for Mathematics, Computing and Cognition (CMCC), Federal University of ABC, S\u00e3o Bernardo do Campo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0439-1534","authenticated-orcid":false,"given":"M. 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