ArticleProceedings of the National Academy of Sciences of the United States of America2010
Evidence for a functional sidedness to the alphabetaTCR.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- The TCR Cα Domain Regulates Responses to Self-pMHC Class II.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Article
- K-Neighbourhood Analysis: A Method for Understanding SMLM Images as Compositions of Local Neighbourhoods.Frontiers in bioinformatics · 2021Article
- Coreceptors and TCR Signaling - the Strong and the Weak of It.Frontiers in cell and developmental biology · 2020Review
- Mechanoimmunology: molecular-scale forces govern immune cell functions.Molecular biology of the cell · 2018Article
- Monomeric TCRs drive T cell antigen recognition.Nature immunology · 2018Article
- Reciprocal TCR-CD3 and CD4 Engagement of a Nucleating pMHCII Stabilizes a Functional Receptor Macrocomplex.Cell reports · 2018Article
- Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes.Journal of immunology (Baltimore, Md. : 1950) · 2017Review
- Article
- A conserved αβ transmembrane interface forms the core of a compact T-cell receptor-CD3 structure within the membrane.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The CD4 and CD3δε Cytosolic Juxtamembrane Regions Are Proximal within a Compact TCR-CD3-pMHC-CD4 Macrocomplex.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Article
- Structural Model of the Extracellular Assembly of the TCR-CD3 Complex.Cell reports · 2016Article
- A Mechanical Switch Couples T Cell Receptor Triggering to the Cytoplasmic Juxtamembrane Regions of CD3ζζ.Immunity · 2015Article
- Identification of the Docking Site for CD3 on the T Cell Receptor β Chain by Solution NMR.The Journal of biological chemistry · 2015Article
- Geometry Dynamics of α -Helices in Different Class I Major Histocompatibility Complexes.Journal of immunology research · 2015Article
- A Transmembrane Domain GGxxG Motif in CD4 Contributes to Its Lck-Independent Function but Does Not Mediate CD4 Dimerization.PloS one · 2015Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
The T cell receptor (TCR) and associated CD3gammaepsilon, deltaepsilon, and zetazeta signaling dimers allow T cells to discriminate between different antigens and respond accordingly, but our knowledge of how these parts fit and work together is incomplete. In this study, we provide additional evidence that the CD3 heterodimers congregate on one side of the TCR in both the alphabeta and gammadeltaTCR-CD3 complexes. We also report that the other side of the alphabetaTCR mediates homotypic alphabetaTCR interactions and signaling. Specifically, an erythropoietin receptor-based dimerization assay was used to show that, upon complex assembly, the CD3epsilon chains of two CD3 heterodimers are arranged side-by-side in both the alphabeta and gammadeltaTCR-CD3 complexes. This system was also used to show that alphabetaTCRs can dimerize in the cell membrane and that mutating the unusual outer strands of the Calpha domain impairs this dimerization. Finally, we present data showing that, for CD4 T cells, the mutations that impair alphabetaTCR dimerization also alter ligand-induced calcium mobilization, TCR accumulation at the site of pMHC contact, and polarization toward the site of antigen contact. These data reveal a "functional-sidedness" to the alphabetaTCR constant region, with dimerization occurring on the side of the TCR opposite from where the CD3 heterodimers are located.
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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.