1.牡丹江医学院公共卫生学院;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
国家重点研发计划(2022YFC2304103)
1.Public Health School,Mudanjiang Medical University;2.State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and epidemiology, Academy of Military Medical Sciences
National Key Research and Development Program of China
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MHC Ⅰ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三个阶段，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HLA I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。
The major histocompatibility complex (MHC) is closely related to immune regulation, and not only has genetic polymorphisms, but also has species differences in MHC restriction. The construction of humanized MHC transgenic mouse models is an important strategy to break through the differences of MHC species and simulate the characteristics of 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. At present, the strategy of knocking out H-2Kb and H-2Db or knocking out murine β2m is adopted to eliminate the competitive inhibition of HLA I molecules by endogenous H-2 class I molecules, and the construction of HLA II transgenic mouse model is to knock out the β strand of murine origin and transfer it to HLA II. class genes.With the optimization of construction strategies, MHC transgenic mouse models have been applied to epitope vaccine development, tumor treatment, and disease genetic association studies, becoming a powerful tool for preclinical trials. In this paper, we summarize the relevant data of MHC transgenic mouse models, and summarize the construction strategies of MHC transgenic mouse models and their application progress in vaccine development and disease treatment.
