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Published on: May 6, 2019
BAG2 Condensates Couple Proteostasis to CD8+T Cell Surveillance
Maria C Almeida1,2, Tian Wang3, Andrew P Longhini1
1Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA.
Biorxiv : the Preprint Server for Biology
|May 7, 2026
Summary
Scientists discovered Immune-Protein Degradation Bodies (I-PDBs) that link protein cleanup with immune responses. These structures help clear toxic protein aggregates, like tau, and present them to T cells, impacting neurodegenerative disease research.
Area of Science:
- Cell Biology
- Immunology
- Neuroscience
Background:
- Protein aggregation, impaired degradation, and immune activation are key features of neurodegenerative diseases.
- The coordination between these processes remains poorly understood.
Purpose of the Study:
- To identify novel mechanisms coordinating proteostasis and immune surveillance.
- To characterize the function of newly discovered Immune-Protein Degradation Bodies (I-PDBs).
Main Methods:
- Utilized cellular models, including those with aggregation-prone tau.
- Investigated the role of BAG2 and Interferon-gamma (IFNγ) in organelle formation.
- Analyzed the composition and function of I-PDBs using proteomic and cellular assays.
Main Results:
- Identified Immune-Protein Degradation Bodies (I-PDBs), BAG2-driven organelles formed at the ER upon IFNγ stimulation.
- I-PDBs concentrate immunoproteasome and MHC-I components, redirecting misfolded proteins from aggresomes.
- Demonstrated that I-PDBs process pathological tau into antigenic peptides, linking proteostasis to CD8+ T cell recognition via the Proteostasis-Associated Immune Relay (PAIR) pathway.
Conclusions:
- I-PDBs represent a novel class of organelles integrating protein quality control with adaptive immunity.
- The PAIR mechanism highlights a direct link between cellular proteostasis and immune surveillance.
- I-PDBs have significant implications for understanding and potentially treating neurodegenerative diseases.
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