Functional Differences Between Two Fc Receptor ITAM Signaling Motifs

• Published in: Blood 1995-11, Vol.86 (9), p.3302-3307
• Main Authors: Herik-Oudijk, Ingrid E.Van den, Bekke, Maarten W.H.Ter, Tempelman, Marielle J., Capel, Peter J.A., Winkel, Jan G.J.Van de
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analysis of the immune response. Humoral and cellular immunity; Animals; Antigen Presentation - drug effects; Base Sequence; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Interleukin-2 - metabolism; Lymphoma, B-Cell; Mice; Molecular Sequence Data; Organs and cells involved in the immune response; Protein Structure, Tertiary; Receptors, IgG - chemistry; Receptors, IgG - physiology; Recombinant Fusion Proteins - pharmacology; Signal Transduction; Structure-Activity Relationship; Tumor Cells, Cultured; Tyrosine - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.9.3302.bloodjournal8693302

Most Ig receptors exist as multi-subunit complexes with a unique ligand binding α chain and a common signaling FcR γ-chain. The myeloid FcγRIIa (CD32) appears unique among FcR because both ligand-binding and signaling capacity are found in the α chain. Within the cytoplasmic tails of FcγRIIa and FcR γ-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyrosines play an important role. Previously, FcγRIIa-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 FcγRIIa, but not in FcR γ-chain receptor complexes. We now assessed the capacity of FcγRIIa wild-type and FcγRIIa/γ 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 FcR γ-chain ITAM, but not the FcγRIIa-ITAM. In addition, FcγRIIa was capable of functional interaction with FcR γ-chain, thus reconstituting the capacity to trigger IL-2 release and antigen presentation. These data document qualitative differences between Fc receptor ITAMs.