Identification of immunodominant IgE binding epitopes of Der p 24, a major allergen of Dermatophagoides pteronyssinus

Abstract

Background The identification of house dust mite (HDM) allergens and epitopes is important for allergy diagnosis and treatment. We sought to identify the Dermatophagoides pteronyssinus group 24 allergen (Der p 24) and to identify its immunodominant IgE epitope(s). Methods Der p 24 cDNA was cloned and expressed in a pET expression system. The IgE binding activity of purified recombinant (r)Der p 24 was evaluated by western blotting. Truncated Der p 24 proteins and overlapping synthetic polypeptides were subjected to IgE binding assays. Balb/c mice were immunized to investigate IgE epitope induction of IgE production. IgE binding of the 32 N-terminal residues of Der p 24 was compared to other Der p epitopes in enzyme-linked immunosorbent assays and dot blot assays. Human skin prick tests (SPTs) were performed. Results We cloned and expressed Der p 24 cDNA (GenBank accession no. KP893174.1). HDM allergic sera bound rDer p 24 in vitro and 5/10 HDM allergic patients (50%) had positive SPT reactions to rDer p 24. The immunodominant IgE epitope of Der p 24 was localized to the N-terminal 32-residue region, which produced a high specific IgE antibody titer in vivo and promoted mast cell β-hexosaminidase release. The IgE binding activity this N-terminal epitope of Der p 24 was stronger than that of Der p 1 or Der p 2 IgE epitopes. Conclusions We identified Der p 24 as a major HDM allergen with strong IgE binding activity via an immunodominant IgE epitope in the N-terminal 32-residue region, which triggers IgE production in vivo. The identified Der p 24 epitope may support HDM allergy diagnosis and treatment.

Identification of immunodominant IgE epitopes of the major house dust mite allergen Der f 24

“…Mutation experiments are required to investigate the importance of the Lys 28 and Tyr 29 residues of Der f 24 for IgE-binding. The results of the present study were similar to that of homolog Der p 24, indicating that the major allergen Group 24 in HDM may share a similar dominant IgE epitope and produce similar clinical significance (25).…”

“…Previously, peptide-displaying phage technology and artificial synthesized peptide scanning technology have been used to identify immunodominant epitopes (37,40). Additionally, our previous study showed that the immunodominant IgE epitopes of Der p 24 located in the N-terminal 32-residue region triggered IgE production in vivo (25). In the present study, artificial hybrid proteins and synthesized polypeptides were used to identify the N-terminal region of Der f 24 as a major mediator of the IgE-binding activity of Der f 24.…”

“…In a multitude of species, UQCRB proteins play an important role in the maintenance of mitochondrial complex III for electron transport and cellular oxygen sensing (24). The only UQCRB proteins that have been reported to exhibit allergenic activity are those from Der f and Der p (25). The Der f and Der p mite species contribute differently to HDM induced allergic disease, potentially due to their differing geographical distributions (26) or inherent characteristic differences between them (18,27).…”

“…The Der f and Der p mite species contribute differently to HDM induced allergic disease, potentially due to their differing geographical distributions (26) or inherent characteristic differences between them (18,27). Importantly, it has been shown previously that Der p 24 exhibits strong IgE-binding activity via an immuno-dominant IgE epitope in its N-terminal 32-residue region (25); however, the dominant IgE epitope of Der f 24 may not be the same as that of its homolog Der p 24, particularly given the differing protein sequences of the two allergens. It remains to be determined how the allergenic properties of the UQCRB protein in Der f differs from and/or resembles the Der p UQCRB protein.…”

Enolase-specific cross antibodies induce neutrophilic inflammation in the intestine

“…The HDM‐specific IgE binds the high‐affinity IgE receptors on the surface of mast cells to make mast cells sensitized. Sensitized mast cells can be activated by re‐exposure to HDM allergens and release pro‐inflammatory mediators, such as histamine, leukotrienes, serotonin, and TNF‐α, to induce inflammation in the local tissues 4 . However, HDM still induces inflammation in the absence of mast cells or IgE receptor‐deficient 5 .…”