| Evidence for a functional sidedness to the alphabetaTCR. | |
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MedLine Citation:
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PMID: 20202921 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Michael S Kuhns; Andrew T Girvin; Lawrence O Klein; Rebecca Chen; Kirk D C Jensen; Evan W Newell; Johannes B Huppa; Björn F Lillemeier; Morgan Huse; Yueh-Hsiu Chien; K Christopher Garcia; Mark M Davis |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-03-02 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-22 Completed Date: 2010-04-22 Revised Date: 2010-09-17 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 5094-9 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, Graduate Program in Immunology, The Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigen-Presenting Cells / cytology Antigens, CD3 / metabolism Calcium Signaling Cell Line Cell Membrane / metabolism Cell Polarity Humans Intracellular Space / metabolism Mice Models, Molecular Mutation / genetics Protein Multimerization Protein Structure, Secondary Protein Subunits / metabolism Receptors, Antigen, T-Cell, alpha-beta / chemistry*, genetics, metabolism* Receptors, Antigen, T-Cell, gamma-delta / metabolism T-Lymphocytes / cytology |
| Grant Support | |
ID/Acronym/Agency:
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//Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD3; 0/Protein Subunits; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/Receptors, Antigen, T-Cell, gamma-delta |
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