Development of HLA bound peptitides which have supressive activity.

开发具有抑制活性的 HLA 结合肽。

• 批准号: 04557027
• 负责人: SASAZUKI Takehiko
• 金额: $ 12.1万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557027/
• 关键词: HLA; Antigenic peptide; Immune response; Transgenic mouse; Genetic polymorphism; DNA typing; MHC; MHC結合性ペプチド; HLA-DP9; トランスフェクタント

There are many diseases caused by abnormal immune responses. To develop the non stimulatory peptide analog that binds to HLA molecule, we investigated the HLA-peptide interactions. Interaction of HLA-DP9 (DPA1*0201/DPB1*0901) molecule and M protein of serotype 12 (SS95/12) streptococcus has been investigated. Seven antigenic peptides restricted by the HLA-DP9 molecule were identified. Comparison of the amino acid sequences among these peptides revealed HLA-DP9-specific binding motif, which differs from the binding motif to the HLA-DR molecules. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to the peptides. This indicated that HLA transgenic mouse should be a useful tool to examine the function of HLA molecules in vivo. We also developed the DNA typing method using PCR/SSOP analysis for HLA-A,HLA-DR,DQ and DP alleles, and found several new alleles. Using this method we determined several susceptible genes for autoimmune disease.

有许多疾病是由异常的免疫反应引起的。为了开发与 HLA 分子结合的非刺激性肽类似物，我们研究了 HLA-肽相互作用。研究了 HLA-DP9 (DPA1*0201/DPB1*0901) 分子与血清型 12 (SS95/12) 链球菌 M 蛋白的相互作用。鉴定出 7 种受 HLA-DP9 分子限制的抗原肽。对这些肽之间的氨基酸序列进行比较揭示了 HLA-DP9 特异性结合基序，该结合基序与 HLA-DR 分子的结合基序不同。在对 HLA-DR51 和 -DQ6 转基因小鼠中 T 细胞对合成肽的反应进行分析时，我们发现 DR51 和 DQ6 转基因小鼠获得了对肽的显着 T 细胞反应。这表明HLA转基因小鼠应该是检查体内HLA分子功能的有用工具。我们还开发了利用PCR/SSOP分析HLA-A、HLA-DR、DQ和DP等位基因的DNA分型方法，并发现了几个新的等位基因。使用这种方法，我们确定了一些自身免疫性疾病的易感基因。

项目成果

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Yoshizumi H 等人：“CD8+ 细胞毒性 T 淋巴细胞的产生，显示出自体抗原呈递细胞的可溶性因子依赖性裂解。”

Fukui Y: "T cell repertoire in a transgenic C57BL/6 mice expressing the HLA-DRA gene on the X chromosome" Immunogenetics. 37. 204-211 (1993)

Fukui Y：“在 X 染色体上表达 HLA-DRA 基因的转基因 C57BL/6 小鼠中的 T 细胞库”免疫遗传学。

Wan XL,et al.: "HLA-A and DRB4 genes in controlling the susceptibility to Hashimoto's Throiditis." Hum, Immunol.(in press).

Wan XL 等人：“HLA-A 和 DRB4 基因控制桥本甲状腺炎的易感性。”

Wan XL, et al: "HLA-A and DRB4 genes in controlling the susceptibility to Hashimoto's Thyroiditis." Hum. Immunol.(in press).

Wan XL 等人：“HLA-A 和 DRB4 基因控制桥本甲状腺炎的易感性。”

Yoshida M,et al.: "DNA typing of HLA-B gene in Takayasu's asteritis." Tissue Antigens.42. 87-90 (1993)

Yoshida M,et al.：“高安星星炎 HLA-B 基因的 DNA 分型。”