ArticleNature2013
Themis sets the signal threshold for positive and negative selection in T-cell development.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 115 citations in OpenAlex.
- p97-mediated proteostasis is a checkpoint for late-stage thymocyte positive selection.Cellular & molecular immunology · 2026Article
- Structural and mechanistic insights into the constitutive Themis-Grb2 complex in T cell signalling.Nature communications · 2026Article
- THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice.The Journal of clinical investigation · 2026Article
- Deviation from physiologically appropriate oxygen levels alters proliferation, cytokine production and proximal antigen receptor signalling in CD4+ memory T cells.Frontiers in immunology · 2026Article
- The role of Themis in development of type 2 diabetes.Research square · 2025Article
- Signature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activation.Nature immunology · 2025Article
- Themis differentially regulates T follicular helper cell differentiation during early and late stages of chronic viral infection.Frontiers in immunology · 2025Article
- METTL3 governs thymocyte development and thymic involution by regulating ferroptosis.Nature aging · 2024Article
- A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice.The Journal of allergy and clinical immunology · 2024Article
- THEMIS promotes T cell development and maintenance by rising the signaling threshold of the inhibitory receptor BTLA.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation.Cellular and molecular life sciences : CMLS · 2024Article
- Mechanism study of ubiquitination in T cell development and autoimmune disease.Frontiers in immunology · 2024Review
- THEMIS is a substrate and allosteric activator of SHP1, playing dual roles during T cell development.Nature structural & molecular biology · 2024Article
- The Function of Ubiquitination in T-Cell Development.Advances in experimental medicine and biology · 2024Review
- Themis controls T cell activation, effector functions, and metabolism of peripheral CD8Life science alliance · 2023Article
- Unrestrained cleavage of Roquin-1 by MALT1 induces spontaneous T cell activation and the development of autoimmunity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Tyrosine Phosphatase Activity of PTPN22 Is Involved in T Cell Development via the Regulation of TCR Expression.International journal of molecular sciences · 2023Article
- A stepwise and digital pattern of RSK phosphorylation determines the outcome of thymic selection.iScience · 2023Article
- A mutation inbioRxiv : the preprint server for biology · 2023Article
- GRB2 promotes thymocyte positive selection by facilitating THEMIS-mediated inactivation of SHP1.The Journal of experimental medicine · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Development of a self-tolerant T-cell receptor (TCR) repertoire with the potential to recognize the universe of infectious agents depends on proper regulation of TCR signalling. The repertoire is whittled down during T-cell development in the thymus by the ability of quasi-randomly generated TCRs to interact with self-peptides presented by major histocompatibility complex (MHC) proteins. Low-affinity TCR interactions with self-MHC proteins generate weak signals that initiate 'positive selection', causing maturation of CD4- or CD8αβ-expressing 'single-positive' thymocytes from CD4(+)CD8αβ(+) 'double-positive' precursors. These develop into mature naive T cells of the secondary lymphoid organs. TCR interaction with high-affinity agonist self-ligands results in 'negative selection' by activation-induced apoptosis or 'agonist selection' of functionally differentiated self-antigen-experienced T cells. Here we show that positive selection is enabled by the ability of the T-cell-specific protein Themis to specifically attenuate TCR signal strength via SHP1 recruitment and activation in response to low- but not high-affinity TCR engagement. Themis acts as an analog-to-digital converter translating graded TCR affinity into clear-cut selection outcome. By dampening mild TCR signals Themis increases the affinity threshold for activation, enabling positive selection of T cells with a naive phenotype in response to low-affinity self-antigens.
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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.