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
曹湘雯 1李敏 2殷琦 2韩雪莲 2王原 2赵光宇1
作者信息
- 1. 牡丹江医学院公共卫生学院,黑龙江牡丹江 157011;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
- 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
- 折叠
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MHC Ⅰ或MHC Ⅱ单转基因小鼠模型和MHCⅠ与MHC Ⅱ双转基因小鼠模型.HLA Ⅰ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-2 Ⅰ类分子对HLAⅠ类分子的竞争性抑制;HLA Ⅱ类转基因小鼠模型的构建则是将鼠源β链敲除,转入HLA Ⅱ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.
Abstract
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 MHC Ⅰ or MHC Ⅱ single-transgenic mouse models and MHC Ⅰ and MHC Ⅱ double-transgenic mouse models.The development of HLA Ⅰ transgenic mouse model went through three stages,at present,the strategy of knocking out H-2Kb and H-2Db or murine β2m is adopted to eliminate the competitive inhibition of HLA Ⅰ molecules by endogenous H-2 class Ⅰ molecules.In the construction of an HLA Ⅱtransgenic mouse model,the β strand of murine origin is knocked out and HLA Ⅱ class 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Key words
major histocompatibility complex/mouse models/immunity/epitope vaccines/oncology treatment引用本文复制引用
基金项目
国家重点研发计划(2022YFC2304103)
出版年
2024
国家科技期刊平台
NSTL
万方数据