Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Immunity Année : 2009

Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor.

Résumé

Despite compromised T cell antigen receptor (TCR) signaling, mice in which tyrosine 136 of the adaptor linker for activation of T cells (LAT) was constitutively mutated (Lat(Y136F) mice) accumulate CD4(+) T cells that trigger autoimmunity and inflammation. Here we show that equipping postthymic CD4(+) T cells with LATY136F molecules or rendering them deficient in LAT molecules triggers a lymphoproliferative disorder dependent on prior TCR engagement. Therefore, such disorders required neither faulty thymic T cell maturation nor LATY136F molecules. Unexpectedly, in CD4(+) T cells recently deprived of LAT, the proximal triggering module of the TCR induced a spectrum of protein tyrosine phosphorylation that largely overlapped the one observed in the presence of LAT. The fact that such LAT-independent signals result in lymphoproliferative disorders with excessive cytokine production demonstrates that LAT constitutes a key negative regulator of the triggering module and of the LAT-independent branches of the TCR signaling cassette.

Domaines

Immunologie

Dates et versions

hal-00432068 , version 1 (13-11-2009)

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Copyright (Tous droits réservés)

Identifiants

Citer

Michael Mingueneau, Romain Roncagalli, Claude Grégoire, Adrien Kissenpfennig, Arkadiusz Miazek, et al.. Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor.. Immunity, 2009, 31 (2), pp.197-208. ⟨10.1016/j.immuni.2009.05.013⟩. ⟨hal-00432068⟩

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