TYROSINE-CONTAINING ACTIVATION MOTIF-DEPENDENT PHAGOCYTOSIS IN MAST-CELLS

FcR capable of triggering cell activation share with BCR and TCR a con served intracytoplasmic tyrosine-containing activation motif (TAM). Be sides cell activation, these receptors trigger other biologic response s, such as endocytosis of soluble ligands. Murine mast cells express t wo types of FcR that, when aggregated by antibodies and multivalent Ag , trigger the release of inflammatory mediators and cytokines. These a re high affinity receptors for IgE (FCepsilonRI) and low affinity rece ptors for IgG (FcgammaRIII). They comprise each an IgE- or IgG-binding alpha-subunit and two TAM-containing subunits that associate with bot h receptors: a beta-subunit and a homodimeric gamma-subunit that can a ssociate also with the other subunits of the TCR. Herein, we focused o n biologic activities triggered in mast cells via the TAM of the gamma -subunits. Using rat basophilic leukemia (RBL) cells stably transfecte d with cDNA-encoding murine FcRIIIalpha, we found that murine FcgammaR III trigger the phagocytosis of antibody-coated erythrocytes. Using RB L transfectants expressing FcgammaRIII with a deletion of the intracyt oplasmic domain of FcgammaRIIIalpha or chimeric receptors having the e xtracellular and transmembrane domains of FcgammaRII and the intracyto plasmic domain of FcgammaRIIIalpha, we showed that intracytoplasmic se quences of FcgammaRIIIalpha are neither necessary nor sufficient for F cgammaRIII to trigger phagocytosis. Using RBL transfectants expressing chimeric receptors having the extracellular and transmembrane domains of FcgammaRII and the TAM-containing intracytoplasmic domain of murin e FcgammaRIIIgamma, we demonstrated that intracytoplasmic sequences of FcgammaRIIIgamma are sufficient to trigger phagocytosis. Using RBL tr ansfectants expressing the same FcgammaRIIIgammma chimeras, in the TAM of which one, the other, or both tyrosine residues were mutated, we e stablished that tyrosines in the TAM sequence are required for phagocy tosis. Our results endow TAMgamma with previously unknown triggering c apacities and FcgammaRIII with new biologic properties.