Počet záznamů: 1
Opposing effects of actin signaling and LFA-1 on establishing the affinity threshold for inducing effector T-cell responses in mice
- 1.
SYSNO ASEP 0473101 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Opposing effects of actin signaling and LFA-1 on establishing the affinity threshold for inducing effector T-cell responses in mice Tvůrce(i) Palmer, E. (CH)
Drobek, Aleš (UMG-J) ORCID
Štěpánek, Ondřej (UMG-J) RID, ORCIDCelkový počet autorů 3 Zdroj.dok. European Journal of Immunology. - : Wiley - ISSN 0014-2980
Roč. 46, č. 8 (2016), s. 1887-1901Poč.str. 5 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova Actin cytoskeleton ; Antigen affinity treshold ; LFA-1 ; Rap1 ; Rho-family GTPases ; T-cell receptor signaling Vědní obor RIV EB - Genetika a molekulární biologie CEP GJ16-09208Y GA ČR - Grantová agentura ČR Institucionální podpora UMG-J - RVO:68378050 UT WOS 000382928300009 DOI https://doi.org/10.1002/eji.201545909 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2017
Počet záznamů: 1