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鉴定中国白癜风患者中新的 HLA-A*0201 限制性 CTL 表位。

Identification of Novel HLA-A*0201-Restricted CTL Epitopes in Chinese Vitiligo Patients.

机构信息

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, shaanxi, 710032, China.

出版信息

Sci Rep. 2016 Nov 8;6:36360. doi: 10.1038/srep36360.

Abstract

Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair. Recent studies suggested the key role of CD8T lymphocytes for mediating immune response in vitiligo through melanocyte differentiation antigens, including tyrosinase, gp100 and MelanA/Mart-1. However, the specific epitopes of these auto-antigens are still unknown. In our study, we predicted the possible HLA-A*0201-restricted nonapeptides overlaying the full-length amino acid sequences of these three known antigens and investigated the lymphocytes reactivity to these nonapeptides by Elispot assay. In addition, we evaluated the abilities of these nonapeptides to activate CD8T cells. We screened out 5 possible epitopes originated from tyrosinase and gp100, numbered P28, P41, P112, P118 and P119. Among these 5 epitopes, notably, P28 and P119 played the dominant role in activating CTLs, with a significant increase in proliferation rate and Interferon-γ (IFN-γ) production of CD8T cells. Nevertheless, antigen-specific T cell reactivity was not detected in MelanA/Mart-1 peptides. Our studies identified two novel epitopes originated from proteins of gp100 and tyrosinase, which may have implications for the development of immunotherapies for vitiligo.

摘要

全身性白癜风是一种自身免疫性疾病,其特征是黑色素细胞丧失,导致皮肤和毛发出现斑驳的色素脱失。最近的研究表明,CD8+T 淋巴细胞通过黑色素细胞分化抗原(包括酪氨酸酶、gp100 和 MelanA/Mart-1)在白癜风的免疫反应中起关键作用。然而,这些自身抗原的特定表位仍不清楚。在我们的研究中,我们预测了这些已知抗原全长氨基酸序列上可能与 HLA-A*0201 结合的九肽,并通过 Elispot assay 研究了淋巴细胞对这些九肽的反应性。此外,我们评估了这些九肽激活 CD8+T 细胞的能力。我们筛选出 5 个可能源自酪氨酸酶和 gp100 的表位,编号为 P28、P41、P112、P118 和 P119。在这 5 个表位中,P28 和 P119 特别在激活 CTL 方面发挥主导作用,CD8+T 细胞的增殖率和干扰素-γ(IFN-γ)产生显著增加。然而,在 MelanA/Mart-1 肽中未检测到抗原特异性 T 细胞反应性。我们的研究确定了源自 gp100 和酪氨酸酶蛋白的两个新表位,这可能对白癜风的免疫治疗发展具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a3/5099573/121199696da8/srep36360-f1.jpg

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