CLEAVAGE OF THE LOW-AFFINITY RECEPTOR FOR HUMAN IGE (CD23) BY A MITE CYSTEINE PROTEASE - NATURE OF THE CLEAVED FRAGMENT IN RELATION TO THE STRUCTURE AND FUNCTION OF CD23

Der p I, a cysteine protease representing a major allergen of the hous e dust mite Dermatophagoides pteronyssinus, has recently been shown to cleave CD23 from the surface of cultured human B cells (RPMI 8866 B c ell line). We have now undertaken a detailed investigation of CD23 cle avage by Der p I. We demonstrate that Del p I cleaves CD23 at two site s (Ser155-Ser156 and Glu298-Ser299) to produce a 17-kDa fragment conta ining the lectin domain and only part of the C-terminal tail. No such effect was demonstrable with mouse CD23, a finding which was anticipat ed based on its lack of the cleavage sites identified on human CD23. B ased on the cleavage pattern and the model of CD23, we propose a seque nce of events leading to the liberation of the 17-kDa soluble CD23 fra gment. The biological significance of such cleavage is underlined by t he demonstration that Der p I-treated B lymphocytes lose their ability to bind IgE, and that the 17-kDa fragment (amino acids 156-298) conta ins the minimum structural requirement (amino acids 156-288) for bindi ng to both IgE and CD21.