Beck Y, Sekimata M, Nakayama S, Müller G A, Müller C A, Yamamoto J, Nagao T, Uchida H, Akiyama N, Kariyone A
Department of Tumor Biology, University of Tokyo, Japan.
Eur J Immunol. 1993 Feb;23(2):467-72. doi: 10.1002/eji.1830230225.
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. The CTL clones could not kill cultured kidney cells. Since cultured kidney cells expressed very low levels of HLA class I antigens it was thought that their failure to be killed by the CTL clones was due to lack of expression of HLA-B35 antigens. After induction of class I antigens on cultured kidney cells by interferon-gamma (IFN-gamma), the IFN-gamma-treated cultured kidney cells were killed by the CTL clones. Furthermore, we isolated hmH antigens as peptides from cultured kidney cells after treatment with IFN-gamma. These results indicate that cultured kidney cells express hmH antigens when HLA class I antigen is induced by IFN-gamma and hmH antigens on cultured kidney cells are recognized by T cells as peptides presented by HLA-B35 molecules.
人类次要组织相容性(hmH)抗原的不相容性可在器官移植中引发移植物排斥反应,并在骨髓移植中引发移植物抗宿主反应。尽管hmH抗原在临床移植中具有重要意义,但对其研究尚不充分。先前的研究已证实hmH抗原在T细胞、B细胞、造血祖细胞和角质形成细胞上表达。我们首次利用HLA - B35限制性、hmH抗原特异性细胞毒性T淋巴细胞(CTL)克隆,证实了培养的肾细胞上hmH抗原的表达,这些CTL克隆先前是从一名排斥来自HLA相同姐妹的两个肾脏的患者中建立的。这些CTL克隆无法杀死培养的肾细胞。由于培养的肾细胞表达的HLA I类抗原水平极低,因此认为它们未被CTL克隆杀死是由于缺乏HLA - B35抗原的表达。在用干扰素 - γ(IFN - γ)诱导培养的肾细胞上的I类抗原后,经IFN - γ处理的培养肾细胞被CTL克隆杀死。此外,在用IFN - γ处理后,我们从培养的肾细胞中分离出作为肽的hmH抗原。这些结果表明,当HLA I类抗原由IFN - γ诱导时,培养的肾细胞表达hmH抗原,并且培养肾细胞上的hmH抗原被T细胞识别为HLA - B35分子呈递的肽。