Tan Shuguang, Lin Nan, Huang Mingxiang, Wang Qing, Tan Yunhong, Li Bingxi, Zhang Ning, Guo Tianling, Cui Yingbin, Chen Xinchao, Wang Dongping, Wang Jue, Xiao Haixia, Liu William J, Yan Jinghua, Zhang Catherine W-H, Liu Cui Hua, Wan Kanglin, Gao George F
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, 102206, China.
Tuberculosis (Edinb). 2017 Dec;107:5-12. doi: 10.1016/j.tube.2017.07.011. Epub 2017 Aug 2.
T cell immune responses have played pivotal roles in host immune protection against Mycobacterium tuberculosis (MTB) infection. MTB specific antigen, Rv3615c (EspC), was identified to be as immunodominant as the well-known ESAT-6 and CFP-10, and has brought promising expectations to more sensitive T-cell based diagnosis and vaccine development. However, limited knowledge about the immunogenicity and diagnostic values of this antigen has restricted its application in clinical practice. Herein, the Rv3615c antigen was identified as a robust CTL immunoantigen with broadly cross-human leucocyte antigen (HLA) allele recognized peptides which may contribute to the broad recognition of Rv3615c antigen among the population. A three-antigen-cocktail (3-Ag-cocktail) comprising of ESAT-6, CFP-10 and Rv3615c was investigated in a multicenter, randomized and double-blinded study to evaluate its clinical diagnostic performances. A significantly improved sensitivity was demonstrated against the 3-Ag-cocktail compared with that against ESAT-6 and CFP-10. Both responsive magnitude and sensitivity were significantly lower in patients concurrently suffering from cancer, indicating its restriction in diagnosis of immunocomprised patients. In conclusion, inclusion of the Rv3615c antigen with multiple HLA restricted CTL epitopes would benefit the T-cell based diagnosis of MTB infection.
T细胞免疫反应在宿主针对结核分枝杆菌（MTB）感染的免疫保护中发挥了关键作用。MTB特异性抗原Rv3615c（EspC）被确定与著名的ESAT-6和CFP-10一样具有免疫显性，这为更敏感的基于T细胞的诊断和疫苗开发带来了令人期待的前景。然而，关于该抗原的免疫原性和诊断价值的知识有限，限制了其在临床实践中的应用。在此，Rv3615c抗原被确定为一种强大的CTL免疫抗原，具有广泛交叉人类白细胞抗原（HLA）等位基因识别的肽段，这可能有助于该抗原在人群中的广泛识别。在一项多中心、随机、双盲研究中，对由ESAT-6、CFP-10和Rv3615c组成的三抗原混合物（3-Ag混合物）进行了研究，以评估其临床诊断性能。与针对ESAT-6和CFP-10相比，针对3-Ag混合物显示出显著提高的敏感性。同时患有癌症的患者的反应强度和敏感性均显著较低，这表明其在免疫功能低下患者诊断中的局限性。总之，包含具有多个HLA限制性CTL表位的Rv3615c抗原将有利于基于T细胞的MTB感染诊断。
