The receptor with high affinity for IgE (FcsigmaRI) is a key molecule in triggering;g the allergic reaction. Therefore understanding its structure and its function is of considerable medical interest and may lead to new therapeutic approaches of allergic diseases. During the past year we have engaged in several types of studies: on the gene structure of FcsigmaRI, studies on the expression of the receptor by gene transfer, studies on the expression of the receptor during cell differentiation, studies on the receptor and IgE binding sites and studies on the structural relationship between FcsigmaRI and Fcgamma receptors. These studies have yielded the following results. 1. With the exception of human beta, cDNA clones for alpha, beta and gamma of FcsigmaRi have now been isolated from three different species: rat, mouse and human. The genomic structure of the human gamma gene has been defined and the chromosomal localization of the subunits has been completed in mice and has begun in humans. 2. By using the techniques of gene transfer, non receptor-bearing cells have been induced to express receptors on their surface. The requirements for cell surface expression are different for the rodent and the human receptor. To understand this difference chimeric (rodent-human) alpha chains and other mutants of alpha have been produced. 3. Receptor expression comes at a very early stage of mouse mast cells' and human basophils' differentiation in IL3-dependent bone marrow cells' cultures. 4. To eventually allow production of crystals to study the receptor binding site, we have engineered truncated human alpha chains which are secreted by COS 7 cells. Production of a stable cell line is in progress. A 76 resudues' peptide derived from the sequence of human IgE was shown to efficiently inhibit the binding of human IgE to human receptors. 5. Fc receptors from mouse macrophages and human NK cells are physically associated with gamma chains identical to those from Fc RI. These gamma chains have been cloned. Their presence is required for the expression of these FcgammaRs in transfected cells.
