The attachment of the Fc region of immunoglobulins to receptors (FcRs) on many cells of the immune system triggers various functions such as phagocytosis, antibody-dependent cytotoxicity, and the secretion of potent mediators. One of these receptors (FcepsilonRI), the high affinity receptor for immunoglobulin E (IgE) plays a central role in immediate allergic reaction. It is a complex structure of an IgE-binding alpha chain, a beta chain and a homodimer of gamma chains. Another of these receptors, the low affinity receptor for immunoglobulin G (FcgammaRIII) is also a multimeric complex which consists of an IgG-binding alpha chain and of gamma chains identical to those found in FcepsilonRI. During the past year, we have engaged in several types of studies involving the gene and subunit structure and the function of these two types of FcRs. These studies have yielded the following results: 1. We have cloned and expressed by transfection cDNAs encoding the human beta chain of FcepsilonRI. The complete genomic organization f the corresponding gene has also been characterized. 2. The promoter region of the human gamma gene has been dissected into several regulatory elements, one of which is a positive element specific of hematopoietic cells. 3. By using the baculovirus system we can produce large amount of truncated alpha chain which contains the high affinity binding site for IgE. We also have expressed successfully the truncated alpha in glycosylation mutants of CHO cells. This material will be used to produce crystals. 4. We have found recently that the receptor subunits become phosphorylated on serine and tyrosine within 5 seconds of receptor engagement. This dual phosphorylation only affects the "activated receptors" and not the adjacent receptors which have not been engaged. Furthermore the receptors are immediately dephosphorylated upon receptor disengagement. 5. We have shown that FcgammaRIII in human NK cells associates with three different types of dimers, gamma, gammazeta and zetazeta. These dimers may be responsible for different signalling pathways. 6. We have discovered that mouse FcgammaRII and FcgammaRIII not only binds IgG with low affinity but also bind IgE with affinities comparable to IgG.