Sequential cooperation of CD2 and CD48 in the buildup of the early TCR signalosome.
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.
Muhammad
Arshad
A
Department of Molecular Immunology, Centre for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria.
Schiller
Herbert B
HB
Forster
Florian
F
Eckerstorfer
Paul
P
Geyeregger
Rene
R
Leksa
Vladimir
V
Zlabinger
Gerhard J
GJ
Sibilia
Maria
M
Sonnleitner
Alois
A
Paster
Wolfgang
W
Stockinger
Hannes
H
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
D015703:Antigens, CD; D018801:CD2 Antigens; D017252:CD3 Complex; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D011948:Receptors, Antigen, T-Cell