Identification of autoantigens recognized by cytotoxic T-cells and responsible for the pathogenesis of aplastic anemia.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Fujita Health University
• Principal Investigator: Akatsuka Yoshiki 藤田保健衛生大学, 医学部, 教授 (70333391)
• Co-Investigator(Kenkyū-buntansha): 葛島 清隆 愛知県がんセンター(研究所), その他部局等, 部長 (30311442)
• Co-Investigator(Renkei-kenkyūsha): NAKAO Shiji 金沢大学, 医薬保健研究域医学系・細胞移植学, 教授 (70217660)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 再生不良性貧血 / 細胞傷害性T細胞 / 自己抗原

Outline of Final Research Achievements

We attempted to identify antigens recognized by HLA-B*40:02-restricted cytotoxic T lymphocytes (CTLs) that might be related to the pathogenesis of aplastic anemia. Because the CTLs exerted cytotoxic activity on K562 cells transduced with HLA-B*40:02, we prepared cDNA libraries from messenger RNA extracted from K562. After extensive screening, a cDNA clone that stimulated interferon-gamma release from one of the CTLs was found. The cDNA was encoded by OS9 whose protein is known to be located in the endoplasmic reticulum and also involved in the hypoxic stress, implicating the potential involvement in the pathogenesis of aplastic anemia. The minimum epitope sequence was composed of 11 amino acids: MAAETLLSSLL. Using the peptide, functional analyses are ongoing. An antigen recognized by another CTL with suppressive function in hematopoietic cells has not been identified, even after screening more than 100,000 cDNA clones.

Free Research Field

血液免疫学