ArticleJournal of immunology (Baltimore, Md. : 1950)2009
The activation threshold of CD4+ T cells is defined by TCR/peptide-MHC class II interactions in the thymic medulla.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Recent insights on the impact of SWELL1 on metabolic syndromes.Frontiers in pharmacology · 2025Review
- Regulatory mechanisms in T cell receptor signalling.Nature reviews. Immunology · 2018Review
- MTOR signaling is essential for the development of thymic epithelial cells and the induction of central immune tolerance.Autophagy · 2018Article
- Myristoylation: An Important Protein Modification in the Immune Response.Frontiers in immunology · 2017Review
- Peripheral residence of naïve CD4 T cells induces MHC class II-dependent alterations in phenotype and function.BMC biology · 2014Article
- A regulatory role for TGF-β signaling in the establishment and function of the thymic medulla.Nature immunology · 2014Article
- Models of self-peptide sampling by developing T cells identify candidate mechanisms of thymic selection.PLoS computational biology · 2013Article
- Subcellular distribution of Lck during CD4 T-cell maturation in the thymic medulla regulates the T-cell activation threshold.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Altered differentiation, diminished pathogenicity, and regulatory activity of myelin-specific T cells expressing an enhanced affinity TCR.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Self-tolerance checkpoints in CD4 T cells specific for a peptide derived from the B cell antigen receptor.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells.Nature immunology · 2011Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Immature thymocytes that are positively selected based upon their response to self-peptide-MHC complexes develop into mature T cells that are not overtly reactive to those same complexes. Developmental tuning is the active process through which TCR-associated signaling pathways of single-positive thymocytes are attenuated to respond appropriately to the peptide-MHC molecules that will be encountered in the periphery. In this study, we explore the mechanisms that regulate the tuning of CD4(+) single-positive T cells to MHC class II encountered in the thymic medulla. Experiments with murine BM chimeras demonstrate that tuning can be mediated by MHC class II expressed by either thymic medullary epithelial cells or thymic dendritic cells. Tuning does not require the engagement of CD4 by MHC class II on stromal cells. Rather, it is mediated by interactions between MHC class II and the TCR. To understand the molecular changes that distinguish immature hyperactive T cells from tuned mature CD4(+) T cells, we compared their responses to TCR stimulation. The altered response of mature CD4 single-positive thymocytes is characterized by the inhibition of ERK activation by low-affinity self-ligands and increased expression of the inhibitory tyrosine phosphatase SHP-1. Thus, persistent TCR engagement by peptide-MHC class II on thymic medullary stroma inhibits reactivity to self-Ags and prevents autoreactivity in the mature repertoire.
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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.