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小鼠H3次要组织相容性复合体免疫显性细胞毒性决定簇的定位克隆与分子特征分析

Positional cloning and molecular characterization of an immunodominant cytotoxic determinant of the mouse H3 minor histocompatibility complex.

作者信息

Zuberi A R, Christianson G J, Mendoza L M, Shastri N, Roopenian D C

机构信息

The Jackson Laboratory, Bar Harbor, Maine 04609, USA.

出版信息

Immunity. 1998 Nov;9(5):687-98. doi: 10.1016/s1074-7613(00)80666-4.

DOI:10.1016/s1074-7613(00)80666-4
PMID:9846490
Abstract

Immune responses to minor histocompatibility antigens are poorly understood and present substantial barriers to successful solid tissue and bone marrow transplantation among MHC-matched individuals. We exploited a unique positional cloning approach relying on the potent negative selection capability of cytotoxic T cells to identify the H3a gene responsible for immunodominant H2-Db-restricted determinants of the classically defined mouse autosomal H3 complex. The allelic basis for reciprocal H3a antigens is two amino acid changes within a single nonamer H2-Db-binding peptide. The H3a gene, now called Zfp106, encodes a 1888-amino acid protein with three zinc fingers and a beta-transducin domain consistent with DNA/protein binding. A region of ZFP106 is identical to a 600-amino acid sequence implicated in the insulin receptor signaling pathway.

摘要

对次要组织相容性抗原的免疫反应了解甚少,并且在MHC匹配个体之间成功进行实体组织和骨髓移植时构成了重大障碍。我们利用了一种独特的定位克隆方法,该方法依赖于细胞毒性T细胞强大的阴性选择能力,以鉴定负责经典定义的小鼠常染色体H3复合体免疫显性H2-Db限制性决定簇的H3a基因。相互H3a抗原的等位基因基础是单个九聚体H2-Db结合肽内的两个氨基酸变化。H3a基因,现称为Zfp106,编码一种含有三个锌指和一个与DNA/蛋白质结合一致的β-转导蛋白结构域的1888个氨基酸的蛋白质。ZFP106的一个区域与胰岛素受体信号通路中涉及的一个600个氨基酸的序列相同。

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