人类主要相容性抗原G的生物学功能与临床移植免疫

Biological function of human leukocyte antigen G and clinical transplantation immunity

人类主要相容性抗原G是非经典人类主要相容性抗原Ⅰ类分子,其免疫抑制特性在临床中显示出两种相反的角色,在妊娠、移植状态下,它的表达下调了机体对胎儿、移植物的免疫反应,起保护作用;在肿瘤和病毒感染时,它的保护作用使得肿瘤细胞和病毒感染细胞逃避免疫系统的抗肿瘤、抗感染,对机体造成了危害。因此,在人类主要相容性抗原G未来的治疗应用中,应当基于两条思路:在器官移植、妊娠障碍方向,通过上调人类主要相容性抗原G及其衍生物的表达并增强其功能,创造一个免疫耐受的微环境,适于移植物、胎儿等的存活和发挥功能。相反,在肿瘤和病毒侵染细胞方向,需要打破肿瘤和病毒的免疫逃逸,对其进行免疫清除,通过RNA干扰封闭人类主要相容性抗原G的表达,或者通过使用人类主要相容性抗原G抗体中和其功能的发挥,毁灭肿瘤和病毒体内存活环境。

Human leukocyte antigen （HLA） G is non-classical HLA class Ⅰ molecule, whose immunosuppressive characteristics display two opposite roles in clinic. Expression of HLA-G can down-regulate the immune response on fetal and graft during pregnancy and transplantation, which is its protection. Under tumor and virus infection, the protection of HLA-G can help tumor cells and virus-infected cells escape from anti-tumor and anti-infection of immune system, which is harmful for body. There should be two thoughts for the clinical application of HLA-G. Up-regulation of the expression and function of HLA-G and its derivatives may be useful to induce a favorable tolerogenic microenvironment for fetal and graft survival in pregnancy disorders and transplantation. In contrast, immune escape of tumor and virus should be broken and immune clearance of tumor cells or virus-infected cells should be carried out. The expression and function of should be blocked by RNA interference or HLA-G antibody in order to damage the surviving environment in vivo of tumor and virus.