ArticleProceedings of the National Academy of Sciences of the United States of America2013
Thymoproteasome subunit-β5T generates peptide-MHC complexes specialized for positive selection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Calibrating T cell responsiveness through interactions with self.Nature reviews. Immunology · 2026Review
- Review
- Proteasome alteration between epithelial and hematopoietic cells facilitates positive selection of CD8 T cells.Nature communications · 2026Article
- Plasticity in the structure and assembly of proteasomes.The Journal of biological chemistry · 2026Review
- Unraveling CD8 lineage decisions reveals that functionally distinct CD8Nature immunology · 2026Article
- Molecular mechanisms in rare proteasomopathies.EULAR rheumatology open · 2026Review
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Proteasome: Role in T Cell Function Regulation.International journal of biological sciences · 2025Review
- Rewiring tumor visibility: The immunopeptidome as a dynamic interface between antigen processing, microenvironmental stress, and immune recognition.Frontiers in oncology · 2025Review
- A journey to your self: The vague definition of immune self and its practical implications.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The thymoproteasome in shaping the CD8Current opinion in immunology · 2023Review
- Tissue-specific proteasomes in generation of MHC class I peptides and CD8Current opinion in immunology · 2022Review
- Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection.Frontiers in immunology · 2022Article
- Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections.Frontiers in immunology · 2022Article
- Effects of sex steroids on thymic epithelium and thymocyte development.Frontiers in immunology · 2022Review
- Peptides for T cell selection in the thymus.Peptides · 2021Review
- Review
- Review
- Specific impact of β5t on proteasome subunit composition in cortical thymic epithelial cells.Cell reports · 2021Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cortical thymic epithelial cells (cTECs) express a unique thymoproteasome subunit-β5T that plays an essential role in the development of CD8 T cells. In contrast, the immunoproteasome subunit-β5i is expressed in other thymic antigen-presenting cells (APCs). The thymoproteasome may generate peptides that are specialized for positive selection, or it may simply serve to generate peptides that are distinct from other APCs that cause negative selection, thereby promoting an overall larger number of surviving clones to mature and function in the immune system. To distinguish these models, we genetically engineered mice to express distinct peptide repertoires in cTECs vs. other APCs without expressing β5T, by generating β5t(5i) knockin mice, in which β5i replaced β5T in cTECs. When such animals were crossed to β5i(-/-) mice, β5i was exclusively expressed in cTECs, whereas β5 was expressed in other cells. However, this mouse did not support normal positive selection, suggesting that β5T generates peptides that are intrinsically better for positive selection (i.e., β5i could not replace β5T) and not merely because these peptides are distinct from peptides presented by other APCs. Finally, using an Nur77(GFP) reporter, we show that the T cells generated in the absence of β5T have higher reactivity to self, generating predominantly CD44(hi) memory phenotype peripheral CD8(+) T cells. Altogether, our results suggest that the thymoproteasome supports positive selection by generating peptides that are optimized for the selection of weakly self-reactive, naïve T-cell clones.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.