ArticleThe Journal of experimental medicine2012
Self-reactive human CD4 T cell clones form unusual immunological synapses.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Effects of High Efficacy Multiple Sclerosis Disease Modifying Drugs on the Immune Synapse: A Systematic Review.Current pharmaceutical design · 2024Pooled it
- Identification of Sjögren's disease-associated T cell receptor motifs through deep sequencing.JCI insight · 2025Article
- Microbial mimics supersize the pathogenic self-response.The Journal of clinical investigation · 2024Article
- Explainable machine learning for profiling the immunological synapse and functional characterization of therapeutic antibodies.Nature communications · 2023Article
- INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control.Communications biology · 2023Article
- Bispecific Antibody Format and the Organization of Immunological Synapses in T Cell-Redirecting Strategies for Cancer Immunotherapy.Pharmaceutics · 2022Review
- T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles.Nature communications · 2022Article
- Beyond GWAS-Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19?International journal of molecular sciences · 2022Article
- The perception and response of T cells to a changing environment are based on the law of initial value.Science signaling · 2022Review
- LFA-1 and kindlin-3 enable the collaborative transport of SLP-76 microclusters by myosin and dynein motors.Journal of cell science · 2021Article
- Overexpression of theJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Nine residues in HLA-DQ molecules determine with susceptibility and resistance to type 1 diabetes among young children in Sweden.Scientific reports · 2021Article
- Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?).Nature reviews. Endocrinology · 2021Review
- Article
- The contribution of thymic tolerance to central nervous system autoimmunity.Seminars in immunopathology · 2021Review
- Next-Generation HLA Sequence Analysis Uncovers Seven HLA-DQ Amino Acid Residues and Six Motifs Resistant to Childhood Type 1 Diabetes.Diabetes · 2020Article
- Relationship of 2D Affinity to T Cell Functional Outcomes.International journal of molecular sciences · 2020Review
- The Role of T Cell Receptor Signaling in the Development of Type 1 Diabetes.Frontiers in immunology · 2020Review
- Article
- A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3Nature immunology · 2019Article
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13 authors at 6 institutions in 1 country.
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Abstract
Recognition of self-peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR-pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease.
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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.