Functional differences between two Fc receptor ITAM signaling motifs.
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.
Van den Herik-Oudijk
I E
IE
Department of Immunology, University Hospital, Utrecht, The Netherlands.
Ter Bekke
M W
MW
Tempelman
M J
MJ
Capel
P J
PJ
Van de Winkel
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D001483:Base Sequence; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D016393:Lymphoma, B-Cell; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017452:Receptors, IgG / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000502:physiology*
D007376:Interleukin-2; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D014443:Tyrosine