Number of the records: 1  

Opposing effects of actin signaling and LFA-1 on establishing the affinity threshold for inducing effector T-cell responses in mice

  1. 1.
    SYSNO ASEP0473101
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleOpposing effects of actin signaling and LFA-1 on establishing the affinity threshold for inducing effector T-cell responses in mice
    Author(s) Palmer, E. (CH)
    Drobek, Aleš (UMG-J) ORCID
    Štěpánek, Ondřej (UMG-J) RID, ORCID
    Number of authors3
    Source TitleEuropean Journal of Immunology. - : Wiley - ISSN 0014-2980
    Roč. 46, č. 8 (2016), s. 1887-1901
    Number of pages5 s.
    Languageeng - English
    CountryUS - United States
    KeywordsActin cytoskeleton ; Antigen affinity treshold ; LFA-1 ; Rap1 ; Rho-family GTPases ; T-cell receptor signaling
    Subject RIVEB - Genetics ; Molecular Biology
    R&D ProjectsGJ16-09208Y GA ČR - Czech Science Foundation (CSF)
    Institutional supportUMG-J - RVO:68378050
    UT WOS000382928300009
    DOI https://doi.org/10.1002/eji.201545909
    AnnotationMature CD8(+) T cells use a narrow antigen affinity threshold to generate tissue-infiltrating cytotoxic effector T cells and induce autoimmune pathology, but the mechanisms that establish this antigen affinity threshold are poorly understood. Only antigens with affinities above the threshold induce stable contacts with APCs, polarization of a T cell, and asymmetric T-cell division. Previously published data indicate that LFA-1 inside-out signaling might be involved in establishing the antigen affinity threshold. Here, we show that subthreshold antigens weakly activate all major distal TCR signaling pathways. Low-affinity antigens are more dependent on LFA-1 than suprathreshold antigens. Moreover, augmenting the inside-out signaling by hyperactive Rap1 does not increase responses to the subthreshold antigens. Thus, LFA-1 signaling does not contribute to the affinity-based antigen discrimination. However, we found that subthreshold antigens do not induce actin rearrangement toward an APC, mediated by Rho-family GTPases, Cdc42, and Rac. Our data suggest that Rac and Cdc42 contribute to the establishment of the antigen affinity threshold in CD8(+) T cells by enhancing responses to high-affinity antigens, or by reducing the responses to low-affinity antigens.
    WorkplaceInstitute of Molecular Genetics
    ContactNikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
    Year of Publishing2017
Number of the records: 1  

  This site uses cookies to make them easier to browse. Learn more about how we use cookies.