CD2 and TCR synergize for the activation of phospholipase Cgamma1/calcium pathway at the immunological synapse.
Upon conjugation with cognate antigen-presenting cells (APCs), T lymphocytes undergo a sustained [Ca(2+)](i) increase resulting from the engagement of TCR and of accessory molecules with ligands expressed on the surface of APCs. We investigated the contribution of the accessory molecule CD2 to the activation of phospholipase Cgamma1 (PLCgamma1)/calcium pathway in antigen-stimulated T cells. We show that CD2 binding with its ligand CD58 expressed on the surface of APCs augments and sustains antigen-induced [Ca(2+)](i) increase in individual T cells interacting with APCs. We also show that in conditions in which CD2-CD58 interaction is impeded, the recruitment of PLCgamma1 to the immunological synapse (IS) is reduced. Interestingly, in these conditions PLCgamma1 phosphorylation in the regulatory tyrosine 783 is also defective. Our results indicate that TCR- and CD2-derived signals converge for the recruitment and activation of PLCgamma1 at the IS and shed new light on the accessory function of CD2 in T cell activation by specific antigen.
Espagnolle
Nicolas
N
INSERM U563, Lymphocyte Interaction Group, Institut Claude de Préval, CHU Purpan, 31059 Toulouse, France.
Depoil
David
D
Zaru
Rossana
R
Demeur
Cecile
C
Champagne
Eric
E
Guiraud
Martine
M
Valitutti
Salvatore
S
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D018801:CD2 Antigens / Q000378:metabolism*; D018968:CD58 Antigens / Q000378:metabolism; D020013:Calcium Signaling; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D008213:Lymphocyte Activation; D018613:Microscopy, Confocal; D051966:Phospholipase C gamma / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism*
D018801:CD2 Antigens; D018968:CD58 Antigens; D011948:Receptors, Antigen, T-Cell; D051746:ZAP-70 Protein-Tyrosine Kinase; D051966:Phospholipase C gamma