【作者】 李州利；

【导师】 洪宝发；

【作者基本信息】 中国人民解放军军医进修学院 ， 外科学， 2006， 博士

【摘要】 1983年Burns等在研究NK细胞杀伤机制的过程中,用从人外周血分离的NK细胞免疫小鼠,得到一株单克隆抗体9.1C3,并发现它能够显著抑制NK细胞对K562细胞的杀伤。1997年Meyaard成功克隆其基因,并命名为白细胞相关免疫球蛋白样受体1(leukocyte-associated immunoglobulin-like recepter-1,LAIR-1)。2004年12月在第八届国际人类白细胞分化抗原会议(HLDA8)上,第四军医大学金伯泉教授与英国牛津大学和澳大利亚纽卡绍尔大学的学者合作提交单克隆抗体,LAIR-1被命名为新的人类白细胞分化抗原CD305。 LAIR-1基因位于人染色体19q13.4上的白细胞免疫球蛋白样受体复合物(leukocyte Ig-like receptor complex,LRC)内,其分子胞膜外区包含有1个免疫球蛋白样结构域,胞浆区含有2个ITIM基序,可募集SHP-1。LAIR-1广泛表达于多种免疫细胞上,包括NK细胞、B细胞、T细胞、单核细胞、树突状细胞及胸腺细胞等。体外研究表明,LAIR-1被其相应的mAb交联后,可传递强烈的抑制性信号,可抑制包括NK细胞、效应T细胞、B细胞和树突状细胞前体等多种免疫细胞的功能。 本实验应用双单克隆抗体夹心ELISA方法对临床器官移植标本sLAIR-1进行检测。在正常人血清和血浆中检测到sLAIR-1分子的存在,比较了血清及血浆中sLAIR-1的含量。在肝、肾移植围手术期患者血清中检测sLAIR-1的变化,并应用流式细胞技更多还原

【Abstract】 LAIR-1/9.1C3 was first discovered in 1983 by Burns’ group based on the monoclonal antibody 9.1C3 raised by immunizing mice with human natural killer （NK） cells and its function that 9.1C3 mAb could inhibit the killing of NK cells against K562 cells. The LAIR-1 gene was cloned in 1997 and was named leukocyte associated immunoglobulin-like recepter-1 （LAIR-1） by Meyaard. During the 8^th international Human Leucocyte Differentiation Antigen Congress held in Dec 2004, LAIR-1 was named CD305 as a novel HLDA after its mAb was referred together by Professor Jin Bo-quan of the Fourth Military Medical University （China） and other experts from Oxford University （Britain） and The University of Newcastle （Australian）.The gene of LAIR-1 was confirmed to be located within the leukocyte Ig-like receptor complex （LRC） on human chromosome 19q13.4. Its extracellular region contains a single Ig-like domain, whereas the cytoplasmic region contains two immunoreceptor tyrosine-based inhibitouy motifs （ITlMs） which can recruit SHP-1. LAIR-1 is expressed generally on many kinds of immunocells including NK cells, T cells, B cells, dendritic cellsand thymus cells. It has been proved in vitro that cross-linking of LAIR-1/9.1C3 by mAb delivers an intensive inhibitory signal which is capable of inhibiting the functions of NK cells, T cells, B cells and dendritic cell precursors.In this experiment, we used the double mAb sandwich ELISA for detecting the level of sLAIR-1 in samples from clinical organ transplantation patients.The sLAIR-1 molecules were detected to exist in serum and plasma of healthy people, and the content was compared between them. In the after operation time of liver transplantation and kidney transplantation, change of sLAIR-1 was examined and was compared with the expression of mLAIR-1 which was detected by flow cytometry. It was found that the level of sLAIR-1 in allograft patients was significantly higher than healthy people and the level of sLAIR-1 was related with the state and stage of these diseases, whereas mLAIR-1 showed the opposite trend. The serum level of sLAIR-1 dramatically rose in the patients who had opposite accidents after liver and kidney transplantation.lt was the 1st time that we detected sLAIR-1 in the bile which outweighed other transplantation immunity associated cytokines on judging rejection and it also had excellent correlation.Our work may contribute to the following study on immune regulation effect and clinical immune apply of sLAIR-1.更多还原