<i>Der p</i> I, a major allergen of the house dust mite, proteolytically cleaves the low‐affinity receptor for human IgE (CD23)

Schulz, Oliver; Laing, Peter; Sewell, Herb F.; Shakib, F

doi:10.1002/eji.1830251131

Cited by 153 publications

(117 citation statements)

References 22 publications

(8 reference statements)

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“…Papain family CPs such as papain itself (33), schistosome Ags (34), house dust mite Der p 1 (35,36), cruzipain from T. cruzi (37), and purified CPB2.8 from L. mexicana can induce Th2 responses (38). In several of these systems, including the L. mexicana CPB enzyme, this immune deviation required enzymatic activity and was not a passive Ag role.…”

Section: Discussionmentioning

confidence: 99%

Cysteine Protease B of Leishmania mexicana Inhibits Host Th1 Responses and Protective Immunity

Buxbaum

Denise

Coombs

et al. 2003

The Journal of Immunology

107

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C3H mice infected with Leishmania mexicana fail to develop a protective Th1 response, and are unable to cure. In this study, we show that L. mexicana cysteine proteases suppress the antileishmanial immune response. Previous studies demonstrated that deletion of the entire multicopy cysteine protease B (CPB) gene array in L. mexicana is associated with decreased parasite virulence, potentially attributable to factors related to parasite fitness rather than to direct effects on the host immune response. We now show that C3H mice infected with the L. mexicana deletion mutant (Δcpb) initially develop lesions that grow at rates comparable to those of wild-type L. mexicana-infected mice. However, in contrast to controls, Δcpb-induced lesions heal with an accompanying Th1 immune response. Lesion resolution was Th1 dependent, as Δcpb-infected IL-12p40−/− and STAT4−/− mice developed high parasite burdens and progressive disease. Moreover, when L. major was transfected with a cosmid expressing multiple L. mexicana CPB genes, this parasite induced a significantly lower IFN-γ response compared with wild-type L. major. These data indicate that cysteine proteases of L. mexicana are critical in suppressing protective immune responses and that inhibition of CPB may prove to be a valuable immunomodulatory strategy for chronic forms of leishmaniasis.

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Section: Discussionmentioning

confidence: 99%

Cysteine Protease B of Leishmania mexicana Inhibits Host Th1 Responses and Protective Immunity

Buxbaum

Denise

Coombs

et al. 2003

The Journal of Immunology

107

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“…52). Upon cleavage, the lectin domain of CD23 was removed, whereas the stalk region remained associated with the cell membrane and retained the ability to bind EBVCS1 (53). Based on their model of the three-dimensional structure of the Fc⑀RII, Schulz et al (54) proposed that the cleavage site is located within the coiled coil region and will therefore only become accessible upon dissociation of the oligomer.…”

Section: Fig 5 Effects Of Ige On Ebvcs1-induced Cd23 Cleavagementioning

confidence: 99%

Binding of Anti-CD23 Monoclonal Antibody to the Leucine Zipper Motif of FcεRII/CD23 on B Cell Membrane Promotes Its Proteolytic Cleavage

Munoz

Brignone

Grenier-Brossette³

et al. 1998

Journal of Biological Chemistry

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In the present study we have compared the binding of two monoclonal antibodies to CD23, EBVCS1 and mAb25, which recognize the stalk and the lectin domain, respectively, on the CD23 molecule. At 4°C, EBVCS1 binds to about 10% of the receptors recognized by mAb25 on the B cell surface. At 37°C, whereas mAb25 reaches its maximal binding within a few seconds, EB-VCS1 requires 60 min to bind to the same extent. Stabilization of the oligomeric structure of CD23 with IgE strongly affects in a dose-dependent fashion the number of binding sites seen by EBVCS1 but not the t 1/2 to reach them, suggesting that EBVCS1 binds to the coiled coil region through an allosteric mechanism. EBVCS1 rapidly down-modulates the membrane CD23 expression with a coincident increase of CD23-soluble fragments in the culture medium, an effect that is inhibited by IgE. In contrast, mAb25, as well as IgE, protects CD23 from proteolytic cleavage and stimulates its endocytosis. These results suggest that EBVCS1 unravels the coiled coil structure of CD23, rendering it more susceptible to proteolytic attack. This supports the oligomeric model proposed previously (Gould, H., Sutton, B., Edmeades, R., and Beavil, A. (1991) Monogr. Allergy 29, 28 -49). The biological significance of these observations is discussed.

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“…Other enzymes cleave the 37-kDa fragments further up the stalk and at a site within the tail to produce progressively smaller fragments containing the head and a portion of the tail (18). A 16-kDa fragment, containing only the lectin domain and 10 amino acids of the tail, results from the digestion of human CD23 by the house dust mite allergen Der p I (21). In addition to the soluble fragments, there are two forms of CD23 that can be expressed in the cell membrane.…”

mentioning

confidence: 99%

Soluble CD23 Monomers Inhibit and Oligomers Stimulate IGE Synthesis in Human B Cells

McCloskey

Hunt

Beavil

et al. 2007

Journal of Biological Chemistry

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The low affinity IgE receptor, CD23, is implicated in IgE regulation and the pathogenesis of allergic disease. CD23 is a type II integral membrane protein, comprising a lectin "head," N-terminal "stalk," and C-terminal "tail" in the extracellular sequence. Endogenous proteases cleave CD23 in the stalk and the tail to release soluble fragments that either stimulate or inhibit IgE synthesis in human B cells. The molecular basis of these paradoxical activities is not understood. We have characterized three fragments of CD23, monomeric derCD23, monomeric exCD23, and oligomeric lzCD23. We show that the monomers inhibit and the oligomer stimulates IgE synthesis in human B cells after heavy chain switching to IgE. CD23 fragments could be targets for therapeutic intervention in allergic disease.

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Der p I, a major allergen of the house dust mite, proteolytically cleaves the low‐affinity receptor for human IgE (CD23)

Cited by 153 publications

References 22 publications

Cysteine Protease B of Leishmania mexicana Inhibits Host Th1 Responses and Protective Immunity

Cysteine Protease B of Leishmania mexicana Inhibits Host Th1 Responses and Protective Immunity

Binding of Anti-CD23 Monoclonal Antibody to the Leucine Zipper Motif of FcεRII/CD23 on B Cell Membrane Promotes Its Proteolytic Cleavage

Soluble CD23 Monomers Inhibit and Oligomers Stimulate IGE Synthesis in Human B Cells

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