Analysis of T cell self-antigen epitope in auto-immune model B/WF1 mice.

自身免疫模型 B/WF1 小鼠 T 细胞自身抗原表位分析。

• 批准号: 04454209
• 负责人: KIMOTO Masao
• 金额: $ 4.1万
• 依托单位: Saga Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General 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/en/grant/KAKENHI-PROJECT-04454209/
• 关键词: T cell self-antigen epitope; B; WF1 mice; H-2 complex; Mixed haplotype; Class II molecule; Peptide motif; Auto-reactive T cell; 病原性T細胞クローン; 抗DNA抗原; SCIDマウス; TCR; 自己ペプチド; 結合ペプチドモチーフ; T細胞クローン; 自己反応性; BW; F1マウス; 自己抗原ペプチド; MHCクラスII分子; ハプロタ

(NZB x NZW) F1 (B/WF1) mice have been studied as an animal model of SLE,a human systemic auto-immune disease. The onset and/or progression of B/WF1 auto-immune symptoms is reported to involve auto-reactive T cells and to be critically related to the heterozygosity of H-2 complex, the murine major histocompatibility complex. We analyzed auto-reactive T cell clones derived from B/WF1 mice. Specificity analysis revealed the presence of mixed haplotype Abetaz/Aalphad class II molecule-restricted auto-reactive T cell clones in B/WF1 mice. Immunoprecipitation and SDS/PAGE analysis usign anti-class II monoclonal antibody revealed that the amount of Abetaz/Aalphad class II molecules is very low compared to conventional class II molecules. Some of the auto-reactive T cell clones induced lgG anti-DNA antibody production upon transfer to young pre-autoimmune B/WF1 mice. DNA sequence analysis of mutant lines derived from transfectant APC that express mutated Abetaz/Aalphad class II molecules revealed that the amino acid at position Aalphad69 is important for the antigen recognition of these auto-reactive T cells. Analysis of bound peptides obtained by HPLC fraction of eluted peptides from affinity purified Abetaz/Aalphad class II molecules revealed a major motif as (I,F)XXXX(M,F,Y).

（NZB x NZW）F1（B/WF1）小鼠已被研究为人类系统性自身免疫性疾病的SLE动物模型。据报道，B/WF1自动免疫症状的发作和/或进展涉及自动反应性T细胞，并且与H-2复合物的杂合性密切相关，H-2复合物是鼠主要的组织相容性复合物。我们分析了源自B/WF1小鼠的自动反应性T细胞克隆。特异性分析表明，B/WF1小鼠中存在混合单倍型Abetaz/Aalphad II类分子限制的自动反应T细胞克隆。免疫沉淀和SDS/PAGE分析USIGN抗类II单克隆抗体表明，与常规II类分子相比，Abetaz/Aalphad II类分子的量非常低。一些自身反应性T细胞克隆转移到年轻的自动免疫前B/WF1小鼠后诱导LGG抗DNA抗体产生。 DNA序列分析来自转染剂APC的突变线，这些突变的ABETAZ/AALPHAD II类分子表明，Aalphad69位置的氨基酸对于对这些自动反应性T细胞的抗原识别很重要。通过亲和力纯化的Abetaz/Aalphad II类分子从HPLC分数获得的结合肽分析显示的主要基序AS（i，f）xxxx（m，f，y）。

项目成果

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Miyake, K.: "Requirement for VLA-4 and VLA-5 integrins in lymphoma cells binding to and migration beneath stromal cells in culture." J.Cell Biol.119. 653-662 (1992)

Miyake, K.：“淋巴瘤细胞中 VLA-4 和 VLA-5 整合素与培养的基质细胞结合并在基质细胞下方迁移的需要。”