Wang Hui, Zheng Xu, Zheng Danyang, Wang Xiaoqian, Zhao Zhiqian, Zhao Mi, Guo Qiang, Mu Yang
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Engineering Research Center of Efficient New Vaccines for Animals, Universities of Shaanxi Province and Ministry of Education, Yangling 712100, China.
Vet Sci. 2024 Oct 7;11(10):483. doi: 10.3390/vetsci11100483.
Lymphocyte activation gene 3 (LAG3) is an inhibitory receptor and the interaction between fibrinogen-like protein 1 and LAG3 can inhibit the anti-tumor effect of T cells both in vivo and in vitro, which was regarded as a new immune evasion mechanism. Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, is an infectious disease characterized by reproductive disorders in pregnant sows and gilts and respiratory problems in pigs of all ages, seriously impacting the pig industry worldwide. In this study, monoclonal antibodies (mAbs) against porcine LAG3 () were developed, and one mAb (1C2) showed good reactivity with on PHA-activated porcine peripheral blood lymphocytes. Epitope mapping showed the epitope recognized by mAb 1C2 was located at amino acid residues 214-435 of . LAG3 expression in the tissues of PRRSV-infected pigs was detected, using mAb 1C2 as the primary antibody, and the results revealed that PRRSV infection caused a marked increase in LAG3 expression compared to the control group. Interference of LAG3 expression on PHA-activated lymphocytes promoted PRRSV replication in the co-culture system of monocyte-derived dendritic cells and lymphocytes, whereas overexpression of LAG3 or blocking of the LAG3 signal with mAb 1C2 inhibited PRRSV replication, indicating that PRRSV infection activates the LAG3-signaling pathway, suggesting that this pathway plays an important role in PRRSV pathogenesis. The results obtained lay the foundation for subsequent research on the role of LAG3 in PRRS and other diseases with persistent infection characteristics.
淋巴细胞激活基因3（LAG3）是一种抑制性受体，纤维蛋白原样蛋白1与LAG3之间的相互作用可在体内和体外抑制T细胞的抗肿瘤作用，这被视为一种新的免疫逃逸机制。由猪繁殖与呼吸综合征病毒（PRRSV）引起的猪繁殖与呼吸综合征（PRRS）是一种传染病，其特征是怀孕母猪和后备母猪出现繁殖障碍，各年龄段猪出现呼吸问题，严重影响全球养猪业。在本研究中，开发了针对猪LAG3的单克隆抗体（mAb），其中一种单克隆抗体（1C2）对PHA激活的猪外周血淋巴细胞上的 显示出良好的反应性。表位作图显示单克隆抗体1C2识别的表位位于 的214 - 435氨基酸残基处。以单克隆抗体1C2为一抗，检测PRRSV感染猪组织中的LAG3表达，结果显示与对照组相比，PRRSV感染导致LAG3表达显著增加。对PHA激活的淋巴细胞上LAG3表达的干扰促进了PRRSV在单核细胞衍生树突状细胞和淋巴细胞共培养系统中的复制，而LAG3的过表达或用单克隆抗体1C2阻断LAG3信号则抑制了PRRSV复制，表明PRRSV感染激活了LAG3信号通路，提示该通路在PRRSV发病机制中起重要作用。所得结果为后续研究LAG3在PRRS以及其他具有持续性感染特征疾病中的作用奠定了基础。
