FUNCTIONAL DIFFERENCES BETWEEN 2 FC RECEPTOR ITAM SIGNALING MOTIFS

Most Ig receptors exist as multi-subunit complexes with a unique ligan d binding alpha chain and a common signaling FcR gamma-chain, The myel oid Fc gamma RIIa (CD32) appears unique among FcR because both ligand- binding and signaling capacity are found in the cu chain. Within the c ytoplasmic tails of Fc gamma RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyro sines play an important role. Previously, Fc gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory functions in I IA1.6 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 gam ma RIIa wild-type and Fc gamma RIIa/gamma chimeric molecules to trigge r IL-2 production and antigen presentation by B cells, Both of these f unctions could solely be triggered by receptors containing the FcR gam ma-chain ITAM, but not the Fc gamma RIIa-ITAM. In addition, Fc gamma R IIa was capable of functional interaction with FcR gamma-chain, thus r econstituting the capacity to trigger IL-2 release and antigen present ation, These data document qualitative differences between Fc receptor ITAMs. (C) 1995 by The American Society of Hematology.