Role of the extracellular domain of FcɛRIα in intracellular processing and surface expression of the high affinity receptor for IgE FcɛRI

The high affinity receptor for immunoglobulin E, FcɛRI, is a critical component of IgE-mediated allergic reactions. It is expressed as a tetramer (αβγ2) made of an IgE-binding α chain and a signaling module formed by the β chain and a dimer of γ chains. It is expressed in humans and rodents on basophils and mast cells at a high level, and, upon activation, it induces the liberation of allergy mediators. In humans a trimeric form lacking the β chain also exists (αγ2). This trimeric form is expressed on antigen presenting cells where it acts to facilitate antigen presentation via IgE. Both the expression and the signaling capacity of the trimer are lower than those of the tetramer. The differences between human (tetrameric and trimeric) and murine (tetrameric only) expression is explained in part by the fact that mouse α cannot be expressed at the cell surface in the absence of β, while human α can. Here we demonstrate that the capacity of human α to be expressed at the cell surface in the absence of β is encoded entirely in its extracellular domain. These findings show that the extracellular domain of the type I transmembrane protein FcɛRI α plays a role in FcɛRI intracellular processing and expression at the cell surface.