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Analysis of molecular basis for allo-recognition

同种异体识别的分子基础分析

基本信息

批准号：
05454212
负责人：
KUROSAWA Yoshikazu
金额：
$ 4.22万
依托单位：
Institute for Comprehensive Medical Science, Fujita Health Univ.
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454212/
关键词：
MHC class I genes cyprinid fish elasmoblanch human MR1 gene evolution MHC遺伝子 MHCクラスI分子免疫の系統発生 PCR 遺伝子ファミリー分子進化組織特異性アロ認識

项目摘要

(1) We have analyzed three genomic genes and three cDNA clones that encode MHC class I molecules in cyprinid fishes, namely the ginbuna crucian carp and the carp. Since these six genes have been isolated by the homology of the sequence of alpha3 domain, the amino acid sequences of the alpha3 domains showed 70-90% identities among them. Based on the extent of homology, they can be classified into four classes. Each of the class consists of several to more than ten members. Thus, this group of MHC genes is composed of 30 to 40 members. Since there are several groups, there are at least 100 genes that encode MHC class I genes in cyprinid fish.(2) We have characterized the genes encoding MHC class I-like molecules in elasmoblanchs (shark).One of the genes encodes a typical class I molecule that consists of three extra-cellular domains. The amino acid sequence of alpha1 and alpha2 domains showed 40 to 50 % identities to those of human HLA and mouse H2. This result idicated that a typical MHC class I gene exists in elasmoblanchs and that the sequences of alpha1 and alpha2 domains have been kept at a high degree during evolution from elasmobranch to mammalian.(3) We have isolated a new gene that encodes MHC class I-like molecule outside of human HLA.While HLA genes are encoded at human chromosome 6, a newly isolated gene, MR1, is encoded at chromosome 1q25. The amino acid sequence of alpha1 and alpha2 of MR1 showed 40 to 50 % identities to those of HLA and mouse H2, even chicken MHC.Since we have already isolated one more gene, MR2, there should be many other genes that encode MHC class I-like genes to be analyzed in human genome. This suggested that the number of MHC genes and their diversification was much larger than expected before.

(1)我们分析了三个基因组基因和三个cDNA克隆编码的MHC I类分子的鲤科鱼类，即银鲫和鲤鱼。由于这6个基因是通过α 3结构域序列的同源性分离出来的，因此α 3结构域的氨基酸序列在它们之间显示出70-90%的同源性。根据同源性的程度，它们可以分为四类。每个班级由几个到十多个成员组成。因此，该组MHC基因由30至40个成员组成。由于有几个群体，鲤科鱼类中至少有100个编码MHC I类基因的基因。(2)本文报道了鲨鱼MHC Ⅰ类分子的编码基因，其中一个基因编码一个典型的由三个胞外结构域组成的MHC Ⅰ类分子。α 1和α 2结构域的氨基酸序列与人HLA和小鼠H2的氨基酸序列显示出40%至50%的同一性。这一结果表明板鳃类动物中存在典型的MHC I类基因，并且在从板鳃类动物进化到哺乳动物的过程中，α 1和α 2结构域的序列高度保持。(3)我们分离到一个新的基因，它编码人类HLA以外的MHC I类分子，而HLA基因编码于人类6号染色体，一个新分离的基因，MR 1，编码于染色体1 q25。MR 1的α 1和α 2氨基酸序列与HLA、小鼠H2、甚至鸡的MHC的氨基酸序列有40 ~ 50%的同源性，既然我们已经分离出了MR 2，那么在人类基因组中应该还有许多编码MHC I类基因的基因有待分析。这表明，MHC基因的数量和它们的多样性远远大于以前的预期。