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

Identification of Novel HLA-A*0201-Restricted CTL Epitopes in Chinese Vitiligo Patients.
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中国白癜风患者中新型 HLA-A*0201 限制性 CTL 表位的鉴定

DOI:
10.1038/srep36360
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发表时间:
2016-11-08
期刊:
影响因子:
4.6
通讯作者:
Gao T
Gao T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cui T;Yi X;Guo S;Zhou F;Liu L;Li C;Li K;Gao T

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泛发性白癜风是一种自身免疫性疾病,其特征是黑素细胞丢失,导致皮肤和毛发斑片状色素脱失。最近的研究表明,CD 8 +T淋巴细胞通过黑素细胞分化抗原,包括酪氨酸酶,gp 100和MelanA/Mart-1介导白癜风的免疫应答的关键作用。然而,这些自身抗原的特异性表位仍然是未知的。在我们的研究中,我们预测了可能的HLA-A*0201限制性九肽覆盖这三个已知抗原的全长氨基酸序列,并研究了淋巴细胞对这些九肽的反应性Elispot分析。此外,我们评估了这些九肽激活CD 8 +T细胞的能力。我们筛选出5个可能的酪氨酸酶和gp 100的表位,编号为P28,P41,P112,P118和P119。在这5个表位中,P28和P119在激活CTL中起主导作用,并显著增加CD 8 +T细胞的增殖率和IFN-γ的产生。然而,在MelanA/Mart-1肽中未检测到抗原特异性T细胞反应性。我们的研究发现了两个新的抗原决定簇,分别来源于gp 100蛋白和酪氨酸酶蛋白,这可能对白癜风免疫治疗的发展具有重要意义。
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 CD8+T 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 CD8+T 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 CD8+T 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.
AHR 启动子变体通过等位基因特异性 AHR-SP1 相互作用调节其转录和下游效应子,充当白癜风的遗传标记
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