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

0473101 - ÚMG 2017 RIV US eng J - Článek v odborném periodiku
Palmer, E. - Drobek, Aleš - Štěpánek, Ondřej
Opposing effects of actin signaling and LFA-1 on establishing the affinity threshold for inducing effector T-cell responses in mice.
European Journal of Immunology. Roč. 46, č. 8 (2016), s. 1887-1901. ISSN 0014-2980. E-ISSN 1521-4141
Grant CEP: GA ČR GJ16-09208Y
Institucionální podpora: RVO:68378050
Klíčová slova: Actin cytoskeleton * Antigen affinity treshold * LFA-1 * Rap1 * Rho-family GTPases * T-cell receptor signaling
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 4.227, rok: 2016

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.
Trvalý link: http://hdl.handle.net/11104/0270266