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

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00473101" target="_blank" >RIV/68378050:_____/16:00473101 - isvavai.cz</a>

  • Result on the web

    <a href="http://dx.doi.org/10.1002/eji.201545909" target="_blank" >http://dx.doi.org/10.1002/eji.201545909</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1002/eji.201545909" target="_blank" >10.1002/eji.201545909</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

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

  • Original language description

    Mature 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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    EB - Genetics and molecular biology

  • OECD FORD branch

Result continuities

  • Project

    <a href="/en/project/GJ16-09208Y" target="_blank" >GJ16-09208Y: T cell receptor signaling and fate decisions made by peripheral T cells in homeostasis and during inflammation</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2016

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    European Journal of Immunology

  • ISSN

    0014-2980

  • e-ISSN

  • Volume of the periodical

    46

  • Issue of the periodical within the volume

    8

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    5

  • Pages from-to

    1887-1901

  • UT code for WoS article

    000382928300009

  • EID of the result in the Scopus database