Abstract
A nonsynonymous single nucleotide polymorphism (SNP) of the low-affinity IgE receptor (FcɛRII/CD23) gene resulting in an arginine to tryptophan exchange at amino-acid position 62 (R62W) has been associated with enhanced T-cell responses to antigen in allergic subjects. To explore the mechanism, a CD23(a) cDNA was cloned into the plasmid pCMVScript-CD23a-C with a C allele (R62). The pCMVScript-CD23a-T with T (W62) was produced using a site-directed mutagenesis approach. The pCMVScript-CD23a-C only (CC), mixture of pCMVScript-CD23a-T and pCMVSCript-CD23a-C (CT) and pCMVScript-CD23a-T only (TT) plasmids were transfected in Cos-7 cells at equivalence in transfection efficiency. No soluble CD23 was released from TT transfectants whereas a higher level of soluble CD23 was detected in CC than in CT transfectants. Human leukocyte elastase (HLE), cathepsin G, the dust mite allergen Der p I and ADAM 33 (A disintegrin and metalloproteinase) were found to cleave membrane CD23 in CC but not in TT transfectants, implying the resistance of CD23 to enzymatic cleavage associated with T mutant. Addition of tunicamycin resulted in the resistance of CD23 to Der p I mediated cleavage in CC but no change in TT transfectants. These results indicate that R62W influences the stability of membrane CD23 molecules due to possibly diminished N-glycosylation.
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Acknowledgements
We appreciate the assistance of Dr James Jones' lab (NJMRC) which provided EBV transformed B cells, of Dr Hongbin Shu's lab (NJMRC) which provided pAAV-lacZ plasmid and of Dr Shelby Umland (Schering-Plough Research Institute) which provided the pcDNA 3.1 ADAM33 plasmid. Dr Dennis Voelker's (NJMRC) advice regarding transfection experiments and the technical contribution of Ms Lin Cao are also appreciated. We are grateful to Dr Edward K Hill (PRA International) for professional editorial assistance and to Dr John Q Wang (UMKC School of Medicine) for reviewing this paper. This work was supported by an American Academy of Allergy, Asthma and Immunology Grant, 2004 AAAAI/Fujisawa Healthcare Allergic Skin Diseases Research Award and National Institute of Health Grant 1U01-GM/HL-61376.
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Meng, JF., McFall, C. & Rosenwasser, L. Polymorphism R62W results in resistance of CD23 to enzymatic cleavage in cultured cells. Genes Immun 8, 215–223 (2007). https://doi.org/10.1038/sj.gene.6364376
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DOI: https://doi.org/10.1038/sj.gene.6364376
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