ArticleThe EMBO journal2011
Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 87 citations in OpenAlex.
- Identification of multiple public TCR repertoires in chronic beryllium disease.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- HLA-DQB1*03:01 strongly affects age of onset of type 1 narcolepsy independently of DQA1 and ethnicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Macrophages and HLA-Class II Alleles in Multiple Sclerosis: Insights in Therapeutic Dynamics.International journal of molecular sciences · 2024Review
- Laboratory Diagnosis of Intrathecal Synthesis of Immunoglobulins: A Review about the Contribution of OCBs and K-index.International journal of molecular sciences · 2024Review
- Non-mutational neoantigens in disease.Nature immunology · 2024Review
- Human thymic putative CD8αα precursors exhibit a biased TCR repertoire in single cell AIRR-seq.Scientific reports · 2023Article
- A dynamic biomimetic model of the membrane-bound CD4-CD3-TCR complex during pMHC disengagement.Biophysical journal · 2023Article
- MHC Class II Presentation in Autoimmunity.Cells · 2023Review
- Exploring Calbindin-IMPase fusion proteins structure and activity.Biochemistry and biophysics reports · 2022Article
- Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines.Frontiers in immunology · 2022Review
- The Many Faces of CD4International journal of molecular sciences · 2020Review
- Peptide-MHC Binding Reveals Conserved Allosteric Sites in MHC Class I- and Class II-Restricted T Cell Receptors (TCRs).Journal of molecular biology · 2020Article
- Geometrical characterization of T cell receptor binding modes reveals class-specific binding to maximize access to antigen.Proteins · 2020Article
- T-cell-receptor cross-recognition and strategies to select safe T-cell receptors for clinical translation.Immuno-oncology technology · 2019Review
- Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic Discrimination of Myelin and Exogenous Antigenic Peptides.Frontiers in immunology · 2019Article
- Article
- HLA variation and disease.Nature reviews. Immunology · 2018Review
- Predicting CD4 T-cell epitopes based on antigen cleavage, MHCII presentation, and TCR recognition.PloS one · 2018Article
- The cytosolic domain of T-cell receptor ζ associates with membranes in a dynamic equilibrium and deeply penetrates the bilayer.The Journal of biological chemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 4 countries.
Funding
Abstract
The failure to eliminate self-reactive T cells during negative selection is a prerequisite for autoimmunity. To escape deletion, autoreactive T-cell receptors (TCRs) may form unstable complexes with self-peptide-MHC by adopting suboptimal binding topologies compared with anti-microbial TCRs. Alternatively, escape can occur by weak binding between self-peptides and MHC. We determined the structure of a human autoimmune TCR (MS2-3C8) bound to a self-peptide from myelin basic protein (MBP) and the multiple sclerosis-associated MHC molecule HLA-DR4. MBP is loosely accommodated in the HLA-DR4-binding groove, accounting for its low affinity. Conversely, MS2-3C8 binds MBP-DR4 as tightly as the most avid anti-microbial TCRs. MS2-3C8 engages self-antigen via a docking mode that resembles the optimal topology of anti-foreign TCRs, but is distinct from that of other autoreactive TCRs. Combined with a unique CDR3β conformation, this docking mode compensates for the weak binding of MBP to HLA-DR4 by maximizing interactions between MS2-3C8 and MBP. Thus, the MS2-3C8-MBP-DR4 complex reveals the basis for an alternative strategy whereby autoreactive T cells escape negative selection, yet retain the ability to initiate autoimmunity.
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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.