title: Sequential cooperation of CD2 and CD48 in the buildup of the early TCR signalosome.
abstract: The buildup of TCR signaling microclusters containing adaptor proteins and kinases is prerequisite for T cell activation. One hallmark in this process is association of the TCR with lipid raft microdomains enriched in GPI-proteins that have potential to act as accessory molecules for TCR signaling. In this study, we show that GPI-anchored CD48 but not CD59 was recruited to the immobilized TCR/CD3 complex upon activation of T cells. CD48 reorganization was vital for T cell IL-2 production by mediating lateral association of the early signaling component linker for activated T cells (LAT) to the TCR/CD3 complex. Furthermore, we identified CD2 as an adaptor linking the Src protein tyrosine kinase Lck and the CD48/LAT complex to TCR/CD3: CD2 associated with TCR/CD3 upon T cell activation irrespective of CD48 expression, while association of CD48 and LAT with the TCR/CD3 complex depended on CD2. Consequently, our data indicate that CD2 and CD48 cooperate hierarchically in the buildup of the early TCR signalosome; CD2 functions as the master switch recruiting CD48 and Lck. CD48 in turn shuttles the transmembrane adapter molecule LAT.
authors.affiliation: Department of Molecular Immunology, Centre for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Arshad
authors.initials: A
authors.lastname: Muhammad
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Schiller
authors.forename: Florian
authors.initials: F
authors.lastname: Forster
authors.forename: Paul
authors.initials: P
authors.lastname: Eckerstorfer
authors.forename: Rene
authors.initials: R
authors.lastname: Geyeregger
authors.forename: Vladimir
authors.initials: V
authors.lastname: Leksa
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.forename: Alois
authors.initials: A
authors.lastname: Sonnleitner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Paster
authors.forename: Hannes
authors.initials: H
authors.lastname: Stockinger
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018801:CD2 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D000071178:CD48 Antigen; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D011485:Protein Binding; D034622:RNA Interference; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D018801:CD2 Antigens; D017252:CD3 Complex; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D011948:Receptors, Antigen, T-Cell