ArticleThe Journal of experimental medicine2010
Peptide-MHC heterodimers show that thymic positive selection requires a more restricted set of self-peptides than negative selection.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- Mechanical force matters in early T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- αβ-T cell receptor transduction gives superior mitochondrial function to γδ-T cells with promising persistence.iScience · 2023Article
- A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function.Nature immunology · 2023Article
- MHC-independent αβT cells: Lessons learned about thymic selection and MHC-restriction.Frontiers in immunology · 2022Review
- Cooperative Stabilization of Close-Contact Zones Leads to Sensitivity and Selectivity in T-Cell Recognition.Cells · 2021Article
- ApoB-Specific CD4Cells · 2021Review
- Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck.Frontiers in immunology · 2021Article
- Adapting T Cell Receptor Ligand Discrimination CapabilityFrontiers in immunology · 2021Review
- CD5 dynamically calibrates basal NF-κB signaling in T cells during thymic development and peripheral activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.Nature immunology · 2019Article
- Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Nonstimulatory peptide-MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling.Nature communications · 2018Article
- TCR Signaling: Mechanisms of Initiation and Propagation.Trends in biochemical sciences · 2018Review
- αβ T cell receptor germline CDR regions moderate contact with MHC ligands and regulate peptide cross-reactivity.Scientific reports · 2016Article
- 2015 Russell Ross Memorial Lecture in Vascular Biology: Protective Autoimmunity in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+) T cells.Nature immunology · 2015Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
T cell selection and maturation in the thymus depends on the interactions between T cell receptors (TCRs) and different self-peptide-major histocompatibility complex (pMHC) molecules. We show that the affinity of the OT-I TCR for its endogenous positively selecting ligands, Catnb-H-2Kb and Cappa1-H-2Kb, is significantly lower than for previously reported positively selecting altered peptide ligands. To understand how these extremely weak endogenous ligands produce signals in maturing thymocytes, we generated soluble monomeric and dimeric peptide-H-2Kb ligands. Soluble monomeric ovalbumin (OVA)-Kb molecules elicited no detectable signaling in OT-I thymocytes, whereas heterodimers of OVA-Kb paired with positively selecting or nonselecting endogenous peptides, but not an engineered null peptide, induced deletion. In contrast, dimer-induced positive selection was much more sensitive to the identity of the partner peptide. Catnb-Kb-Catnb-Kb homodimers, but not heterodimers of Catnb-Kb paired with a nonselecting peptide-Kb, induced positive selection, even though both ligands bind the OT-I TCR with detectable affinity. Thus, both positive and negative selection can be driven by dimeric but not monomeric ligands. In addition, positive selection has much more stringent requirements for the partner self-pMHC.
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