Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8+ T cells
Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8+ T cells
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DOI：
10.1111/j.1365-2249.2004.00600.x
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发表时间：
2004-10-01
影响因子：
4.6
通讯作者：
Valdimarsson, H
中科院分区：
文献类型：
--
作者：
Johnston, A;Gudjonsson, JE;Valdimarsson, H
银屑病与化脓性链球菌咽喉部感染的关联提示了已知浸润银屑病皮肤的T细胞的潜在抗原靶点。链球菌M蛋白与人表皮角蛋白具有广泛的序列同源性。角蛋白17（K17），而大多是不存在于未涉及的皮肤，是上调银屑病病变。因此，M蛋白引发的T细胞可以通过分子模拟识别上调的角蛋白表位。使用体外淋巴细胞培养和细胞因子流式细胞术，我们证明HLA-Cw*0602（+）银屑病患者对基于序列同源性和预测的HLA-Cw*0602结合选择的K17和M6蛋白的肽具有显著的CD 8（+）T细胞干扰素（IFN）-γ应答。这些反应在皮肤归巢的皮肤淋巴细胞相关抗原表达（CLA（+））CD 8（+）T细胞亚群中的频率约为10倍。CD 4（+）T细胞仅显示临界反应。来自Cw 6（+）非银屑病个体的CLA（+）CD 8（+）T细胞对一些M6肽应答，但很少对K17肽应答。Cw 6（-）银屑病患者表现出的反应介于Cw 6（+）患者和对照组之间。这些发现表明银屑病患者具有识别角蛋白自身抗原的CD 8（+）T细胞，链球菌M蛋白和人角蛋白共有的表位可能是浸润银屑病皮损的CD 8（+）T细胞的靶点。
The association of psoriasis with Streptococcus pyogenes throat infections suggests a potential antigenic target for the T cells that are known to infiltrate psoriatic skin. Streptococcal M protein share an extensive sequence homology with the human epidermal keratins. Keratin 17 (K17), while being mostly absent from uninvolved skin, is up-regulated in psoriatic lesions. Consequentially, M-protein-primed T cells may recognize up-regulated keratin epitopes via molecular mimicry. Using in vitro lymphocyte culture and cytokine flow cytometry we demonstrate that HLA-Cw*0602(+) psoriasis patients had significant CD8(+) T cell interferon (IFN)-gamma responses to peptides from the K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. These responses were about 10 times more frequent in the skin-homing cutaneous lymphocyte-associated antigen-expressing (CLA(+)) subset of CD8(+) T cells. CD4(+) T cells showed only borderline responses. CLA(+) CD8(+) T cells from Cw6(+) non-psoriatic individuals responded to some M6 peptides but rarely to K17 peptides. Cw6(-) psoriasis patients showed a response that was intermediate between Cw6(+) patients and controls. These findings indicate that psoriatic individuals have CD8(+) T cells that recognize keratin self-antigens and that epitopes shared by streptococcal M proteins and human keratins may be targets for the CD8(+) T cells that infiltrate psoriatic skin lesions.