1. Functional differences between two Fc receptor ITAM signaling motifs.
- Author
-
Van den Herik-Oudijk IE, Ter Bekke MW, Tempelman MJ, Capel PJ, and Van de Winkel JG
- Subjects
- Amino Acid Sequence, Animals, Antigen Presentation drug effects, Base Sequence, Humans, Interleukin-2 metabolism, Lymphoma, B-Cell, Mice, Molecular Sequence Data, Protein Structure, Tertiary, Receptors, IgG chemistry, Recombinant Fusion Proteins pharmacology, Structure-Activity Relationship, Tumor Cells, Cultured, Receptors, IgG physiology, Signal Transduction, Tyrosine physiology
- Abstract
Most Ig receptors exist as multi-subunit complexes with a unique ligand binding alpha chain and a common signaling FcR gamma-chain. The myeloid Fc gamma RIIa (CD32) appears unique among FcR because both ligand-binding and signaling capacity are found in the alpha chain. Within the cytoplasmic tails of Fc gamma RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyrosines play an important role. Previously, Fc gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory functions in IIA1.6 B-cell transfectants. Triggering of interleukin-2 (IL-2) release and antigen presentation was absent in Fc gamma RIIa, but not in FcR gamma-chain receptor complexes. We now assessed the capacity of Fc gamma RIIa wild-type and Fc gamma RIIa/gamma chimeric molecules to trigger IL-2 production and antigen presentation by B cells. Both of these functions could solely be triggered by receptors containing the FcRIIa was capable of functional interaction with FcR gamma-chain, thus reconstituting the capacity to trigger IL-2 release and antigen presentation. These data document qualitative differences between Fc receptor ITAMs.
- Published
- 1995