The analysis of molecular mechanisms of autoimmune thyroid diseases

T细胞抗原表位的鉴定是揭示自身免疫性甲状腺疾病病因的关键。我们以前曾报道过Graves病与HLA-A^<**>0206有关，桥本甲状腺炎与HLA-A^<**>0207有关。我们还发现，等位基因特异性肽基序，包括占主导地位的锚氨基酸残基之间的这些HLA-A2亚型有很大的不同。基于HLA-A ** 0206结合基序，我们合成了符合该基序的TSHR肽，并检测了针对这些肽的T细胞应答。然而，我们找不到任何答复。肽库方法包括所有可能的肽序列，为检测T细胞识别的抗原肽提供了潜在的强大工具。接下来，我们合成了包括20^9种肽种类的肽混合物，并评估了文库方法研究细胞毒性T细胞（CTL）特异性的有效性。我们发现，混合肽能够从健康供体扩增T细胞，并具有肽特异性细胞毒性，这表明文库方法提供了用于监测自身免疫性甲状腺肿中T细胞特异性的有力工具。

The identification of T cell antigen epitopes is critical to reveal the etiology of autoimmune thyroid diseases. We have previously reported that Graves' disease are associated with HLA-A^<**>0206 and Hashimoto's thyroiditis are associated with HLA-A^<**>0207. We have also revealed that the allele-specific peptide-motifs including the dominant anchor amino acid residues were considerably different among these HLA-A2 subtypes. Based on the HLA-A^<**>0206 binding motif we synthesized peptides of TSHR which fit the motif and examined the T cell response against these peptides. However, we could not find any responses. Peptide library methods, which include all possible peptide sequences offer a potentially powerful tool for the detection of antigenic peptides recognized by T cells. We next synthesized the peptide mixtures including 20^9 peptide species and evaluated the effectiveness of the library method to investigate the specificity of cytotoxic T cells (CTL). We found that the mixture peptides are able to expand T cells from healthy donors and have peptides specific cytotoxicity suggesting that the library methods presents a powerful tool for monitoring specificity of T cells in autoimmune thyroid grands.