title: Impaired activation and localization of LAT in anergic T cells as a consequence of a selective palmitoylation defect.
abstract: The molecular basis of T cell anergy is not completely understood. We show that in antigen-primed anergic murine CD4(+) T cells the linker for activation of T cells (LAT) is hypophosphorylated upon CD3/CD28 restimulation. Signaling events downstream of LAT (PLCgamma1 phosphorylation and p85 [PI3-K] association) were impaired, whereas upstream events (CD3zeta and ZAP-70 phosphorylation) remained intact. LAT recruitment to the immunological synapse and its localization in detergent-resistant membrane (DRM) fractions were defective in anergic T cells. These defects resulted from impaired palmitoylation of LAT and were selective since the DRM localization and palmitoylation of Fyn were intact. This LAT defect was independent of Cbl-b and did not reflect enhanced LAT degradation. These results identify LAT as the most upstream target of anergy induction; moreover, they suggest that regulation of the amount of LAT in the immunological synapse and DRM by posttranslational palmitoylation contributes to the induction of T cell anergy.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hundt
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tabata
authors.forename: Myung-Shin
authors.initials: MS
authors.lastname: Jeon
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Roma
authors.initials: R
authors.lastname: Krishna
authors.forename: Lauren
authors.initials: L
authors.lastname: De Giorgio
authors.forename: Yun-Cai
authors.initials: YC
authors.lastname: Liu
authors.forename: Masaki
authors.initials: M
authors.lastname: Fukata
authors.forename: Amnon
authors.initials: A
authors.lastname: Altman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017635:Clonal Anergy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell