MHC功能及其转基因小鼠模型的研究进展  

Progress of research on MHC function and transgenic mouse models

作　　者：曹湘雯 李敏[2] 殷琦 韩雪莲 王原 赵光宇 CAO Xiangwen;LI Min;YIN Qi;HAN Xuelian;WANG Yuan;ZHAO Guangyu(Public Health School,Mudanjiang Medical University,Mudanjiang 157011;China.2.State Key Laboratory of Pathogen and Biosecurity,Institute of Microbiology and Epidemiology,Academy of Military Medical Sciences,Beijing 100071)

机构地区：[1]牡丹江医学院公共卫生学院,黑龙江牡丹江157011 [2]军事科学院军事医学研究院微生物流行病研究所,病原微生物生物安全全国重点实验室,北京100071

出　　处：《中国比较医学杂志》2024年第6期151-160,共10页Chinese Journal of Comparative Medicine

基　　金：国家重点研发计划(2022YFC2304103)。

摘　　要：主要组织相容性复合体(major histocompatibility complex, MHC)与机体免疫调节密切相关,不仅具有遗传多态性,而且MHC限制性存在种属差异。人类的MHC被称为人白细胞抗原(human leukocyte antigen, HLA),小鼠MHC则被称为H-2。构建人源化MHC转基因小鼠模型是突破MHC种属差异并模拟人体免疫应答特征的重要策略。MHC转基因小鼠主要分为MHCⅠ或MHCⅡ单转基因小鼠模型和MHCⅠ与MHCⅡ双转基因小鼠模型。HLAⅠ类转基因小鼠模型发展经历了3个阶段,目前采取敲除H-2Kb和H-2Db或者敲除鼠源β2m的策略来消除内源的H-2Ⅰ类分子对HLAⅠ类分子的竞争性抑制;HLAⅡ类转基因小鼠模型的构建则是将鼠源β链敲除,转入HLAⅡ类基因。随着构建策略的优化,MHC转基因小鼠模型被应用于表位疫苗研发、肿瘤治疗及疾病遗传关联研究中,成为临床前试验的有力工具。本文对MHC转基因小鼠模型相关资料进行了总结,概述了MHC转基因小鼠模型的构建策略及其在疫苗研发、疾病治疗等方面的应用进展。The major histocompatibility complex(MHC)is closely related to immune regulation.MHC shows distinct genetic polymorphism,and there are also species differences in MHC restriction.The human MHC is called human leukocyte antigen(HLA),and the mouse MHC is called H-2.The construction of humanized MHC transgenic mouse models is an important strategy to overcome the differences in MHC among species and simulate the characteristics of a human immune response.MHC transgenic mice are mainly divided into MHCⅠor MHCⅡsingle-transgenic mouse models and MHCⅠand MHCⅡdouble-transgenic mouse models.The development of HLAⅠtransgenic mouse model went through three stages,at present,the strategy of knocking out H-2K b and H-2D b or murineβ2m is adopted to eliminate the competitive inhibition of HLAⅠmolecules by endogenous H-2 classⅠmolecules.In the construction of an HLAⅡtransgenic mouse model,theβstrand of murine origin is knocked out and HLAⅡclass genes are inserted.With the optimization of construction strategies,MHC transgenic mouse models have been applied to epitope vaccine development,tumor treatment,and genetic disease-association studies,becoming a powerful tool for preclinical trials.In this paper,we summarize the relevant data on MHC transgenic mouse models,as well as the construction strategies used for MHC transgenic mouse models and their application in vaccine development and disease treatment.

关 键 词：主要组织相容性复合体 小鼠模型 免疫 表位疫苗 肿瘤治疗 

分 类 号：R-33[医药卫生]