• Login
    View Item 
    •   Home
    • Research from April 2016
    • Biomedical and biological science
    • View Item
    •   Home
    • Research from April 2016
    • Biomedical and biological science
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UOBREPCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalDepartmentThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalDepartment

    My Account

    LoginRegister

    About

    AboutLearning ResourcesResearch Graduate SchoolResearch InstitutesUniversity Website

    Statistics

    Display statistics

    Peptide-specific, TCR-alpha-driven, coreceptor-independent negative selection in TCR alpha-chain transgenic mice

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Furmanski, Anna L.
    Bartok, Istvan
    Chai, Jian-Guo
    Singh, Yogesh
    Ferreira, Cristina
    Scott, Diane
    Holland, Stephen J.
    Bourdeaux, Christophe
    Crompton, Tessa
    Dyson, Julian
    Issue Date
    2010-01-06
    Subjects
    TCR-α
    C550 Immunology
    
    Metadata
    Show full item record
    Abstract
    As thymocytes differentiate, Ag sensitivity declines, with immature CD4-CD8- double-negative (DN) cells being most susceptible to TCRsignaling events. We show that expression of alphabetaTCR from the DN3 stage lowers the threshold for activation, allowing recognition of MHC peptides independently of the TCR beta-chain and without either T cell coreceptor. The MHC class I-restricted C6 TCR recognizes the Y-chromosome-derived Ag HYK(k)Smcy. Positive selection in C6 alphabetaTCR females is skewed to the CD8 compartment, whereas transgenic male mice exhibit early clonal deletion of thymocytes. We investigated the effect of the HYK(k)Smcy complex on developing thymocytes expressing the C6 TCR alpha-chain on a TCR-alpha(-/-) background. On the original selecting haplotype, the skew to the CD8 lineage is preserved. This is MHC dependent, as the normal bias to the CD4 subset is seen on an H2b background. In male H2k C6 alpha-only mice, the presence of the HYK(k)Smcy complex leads to a substantial deletion of thymocytes from the DN subset. This phenotype is replicated in H2k C6 alpha-only female mice expressing an Smcy transgene. Deletion is not dependent on the beta variable segment of the C6 TCR or on a restricted TCR-beta repertoire. In contrast, binding of HYK(k)Smcy and Ag-specific activation of mature CD8+ T cells is strictly dependent on the original C6 beta-chain. These data demonstrate that, in comparison with mature T cells, alphabetaTCR+ immature thymocytes can recognize and transduce signals in response to specific MHC-peptide complexes with relaxed binding requirements.
    Citation
    Furmanski AL, Bartok I, Chai J, Singh Y, Ferreira C, Scott D, Holland SJ, Bourdeaux C, Crompton T, Dyson J (2010) 'Peptide-specific, TCR-alpha-driven, coreceptor-independent negative selection in TCR alpha-chain transgenic mice', Journal of Immunology, 184 (2), pp.650-657.
    Publisher
    American Association of Immunologists
    Journal
    Journal of Immunology
    URI
    http://hdl.handle.net/10547/623396
    DOI
    10.4049/jimmunol.0902291
    PubMed ID
    19995903
    Additional Links
    http://www.jimmunol.org/cgi/content/full/184/2/650
    Type
    Article
    Language
    en
    ISSN
    0022-1767
    ae974a485f413a2113503eed53cd6c53
    10.4049/jimmunol.0902291
    Scopus Count
    Collections
    Biomedical and biological science

    entitlement

    Related articles

    • Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats.
    • Authors: Mitnacht R, Bischof A, Torres-Nagel N, Hünig T
    • Issue date: 1998 Jan 15
    • Examination of thymic positive and negative selection by flow cytometry.
    • Authors: Hu Q, Nicol SA, Suen AY, Baldwin TA
    • Issue date: 2012 Oct 8
    • The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes.
    • Authors: Penninger JM, Sirard C, Mittrücker HW, Chidgey A, Kozieradzki I, Nghiem M, Hakem A, Kimura T, Timms E, Boyd R, Taniguchi T, Matsuyama T, Mak TW
    • Issue date: 1997 Aug
    • Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability, improves TCR assembly, and parallels other indicators of positive selection.
    • Authors: Kearse KP, Takahama Y, Punt JA, Sharrow SO, Singer A
    • Issue date: 1995 Jan 1
    • The quantity of TCR signal determines positive selection and lineage commitment of T cells.
    • Authors: Watanabe N, Arase H, Onodera M, Ohashi PS, Saito T
    • Issue date: 2000 Dec 1
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.