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ANALYSIS OF ALLOANTIGENIC PEPTIDES

同种异体抗原肽的分析

基本信息

批准号：
05807103
负责人：
BECK Yoshifumi
金额：
$ 1.15万
依托单位：
UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
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-05807103/
关键词：
alloantigenic peputides minor histocompatibility antigen HLA-B35 CTL HLA-B51 トランスジェニックマウス HLA

项目摘要

Incompatibility of human minor histocompatibility (hmH) antigens can induce rejection of grafts in organ transplantation and graft-versus-host reactions in bone marrow transplantation. In spite of their importance in clinical transplantation, hmH antigens are not well studied. Previous studies have demonstrated the expression of hmH antigens on T and B cells, hematopoietic progenitor cells and keratinocytes. We have for the first time demonstrated the expression of hmH antigens on cultured kidney cells using HLA-B35-restricted, hmH antigen-specific cytotoxic T lymphocyte (CTL) clones, which were previously established from a patient who rejected two kidneys from HLA-identical sisters.To investigate the polymorphism of human minor histocompatibility (mH) antigens, PBLs from 23 Japanese individuals and 25 German individuals with HLA-B35 were studied by using four human mH antigen-specific, HLA-B35-restricted CTL clones. The CTL clones killed PHA-stimulated PBLs from all 23 Japanese individuals. On the other hand, they killed the PHA-stimulated PBLs from 19 of 25 German individuals and partially killed the PHA-stimulated PBLs from three German individuals (CTL weakly sensitive cell line) ; those from another three individuals (CTL-resistant cell line) were not killed by the CTL clones. All of three CTL weakly sensitive cell lines carry HLA-B^*3503 molecules, whereas the three CTL-resistant cell lines carry HLA-B^*3502, B^*3507, and B^*3508 molecules. Thus, the presentation of minor H antigen was affected by the aminoacid substitutions of peptide binding groove in HLA class l morecules.

人类次要组织相容性（hmH）抗原的不相容性可诱发器官移植中的移植物排斥和骨髓移植中的移植物抗宿主反应。尽管 hmH 抗原在临床移植中很重要，但尚未得到充分研究。先前的研究已证明 hmH 抗原在 T 细胞和 B 细胞、造血祖细胞和角质形成细胞上表达。我们首次使用 HLA-B35 限制性 hmH 抗原特异性细胞毒性 T 淋巴细胞 (CTL) 克隆证明了培养肾细胞上 hmH 抗原的表达，该克隆先前是从一名拒绝 HLA 相同姐妹的两个肾脏的患者中建立的。为了研究人类次要组织相容性 (mH) 抗原的多态性，来自 23 个日本人的 PBL 通过使用四种人类 mH 抗原特异性、HLA-B35 限制性 CTL 克隆，对患有 HLA-B35 的个体和 25 名德国个体进行了研究。 CTL 克隆杀死了所有 23 个日本个体中 PHA 刺激的 PBL。另一方面，他们杀死了25个德国个体中19个的PHA刺激的PBL，并部分杀死了3个德国个体（CTL弱敏感细胞系）的PHA刺激的PBL；来自另外三个个体（CTL 抗性细胞系）的细胞没有被 CTL 克隆杀死。所有三种CTL弱敏感细胞系均携带HLA-B^*3503分子，而三种CTL抗性细胞系均携带HLA-B^*3502、B^*3507和B^*3508分子。因此，次要H抗原的呈递受到HLA I类羊肚菌中肽结合沟的氨基酸取代的影响。