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 house dust mite Dermatophagoides pteronyssinus, has recently been shown to cleave CD23 from the surface of cultured human B cells (RPMI 8866 B cell line). We have now undertaken a detailed investigation of CD23 cleavage by Der p I. We demonstrate that Der p I cleaves CD23 at two sites (Ser155-Ser156 and Glu298-Ser299) to produce a 17-kDa fragment containing the lectin domain and only part of the C-terminal tail. No such effect was demonstrable with mouse CD23, a finding which was anticipated based on its lack of the cleavage sites identified on human CD23. Based on the cleavage pattern and the model of CD23, we propose a sequence of events leading to the liberation of the 17-kDa soluble CD23 fragment. The biological significance of such cleavage is underlined by the demonstration that Der p I-treated B lymphocytes lose their ability to bind IgE, and that the 17-kDa fragment (amino acids 156-298) contains the minimum structural requirement (amino acids 156-288) for binding to both IgE and CD21.
Schulz
O
O
Division of Molecular & Clinical Immunology, University of Nottingham, GB.
Sutton
B J
BJ
Beavil
R L
RL
Shi
J
J
Sewell
H F
HF
Gould
H J
HJ
Laing
P
P
Shakib
F
F
D000818:Animals; D039741:Antigens, Dermatophagoides; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D051379:Mice; D008925:Mites / Q000201:enzymology* / Q000276:immunology; D008958:Models, Molecular; D008970:Molecular Weight; D017464:Receptors, Complement 3d / Q000378:metabolism; D017455:Receptors, IgE / Q000737:chemistry / Q000378:metabolism*
D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases