Competing functions encoded in the allergy-associated FcεRIβ gene

Allergic reactions are triggered via crosslinking of the high-affinity receptor for immunoglobulin E, FcepsilonRI. In humans, FcepsilonRI is expressed as a tetramer (alphabetagamma(2)) and a trimer (alphagamma(2)). The beta subunit is an amplifier of FcepsilonRI surface expression and signaling. Here, we show that as a consequence of alternative splicing, the FcepsilonRIbeta gene encodes two proteins with opposing and competing functions. One isoform is the full-length classical beta, the other a novel truncated form, beta(T). In contrast to beta, beta(T) prevents FcepsilonRI surface expression by inhibiting alpha chain maturation. Moreover, beta(T) competes with beta to control FcepsilonRI surface expression in vitro. We propose that the relative abundance of the products of the beta gene may control the level of FcepsilonRI surface expression and thereby influence susceptibility to allergic diseases.