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J Invest Dermatol. 2018 Sep;138(9):1917-1924. doi: 10.1016/j.jid.2018.03.1515. Epub 2018 Mar 26.

Identification of Immunodominant Th2-Cell Epitopes in Chinese Patients with Bullous Pemphigoid.

Author information

1
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
2
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: xjwgang@fmmu.edu.cn.

Abstract

Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease caused by autoantibodies targeting the juxtamembranous extracellular noncollagenous 16A (NC16A) domain of human collagen XVII (also known as BP180). Because T-helper (Th) cells are essential for antibody responses to antigens, we adopted an assay to map the immunodominant Th2-cell epitopes in NC16A. We synthesized 22 overlapping peptides spanning the entire sequence of BP180-NC16A and investigated the reactivity of Th2 cells from patients with BP to these peptides using the Enzyme-Linked ImmunoSpot (ELISPOT) assay. We screened two epitope peptides, P2 (492-506 aa: VRKLKARVDELERIR) and P5 (501-515 aa: ELERIRRSILPYGDS), and confirmed that these epitopes play a dominant role in stimulating CD4+ T-cell proliferation and Th2 IL-4 cytokine production, and activating B cells to secrete autoantibodies. These immunodominant epitopes are HLA-DR-restricted and were observed in subjects with different HLA alleles. This work contributes to elucidation of the epitope-mediated immunologic pathogenesis of BP, and the identified Th2-cell epitopes are candidates for epitope-specific therapeutic strategy.

PMID:
29588155
DOI:
10.1016/j.jid.2018.03.1515
[Indexed for MEDLINE]

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