Veterans Administration Portland Health Care System, Research & Development, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA.
Oregon Health & Sciences University, Department of Pulmonary and Critical Care Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Sci Rep. 2017 Jul 4;7(1):4622. doi: 10.1038/s41598-017-04894-0.
Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. Both classically and non-classically restricted cytotoxic CD8 T cells are important to the control of Mtb infection. We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8 T cells. In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8 T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. Recognition by the CD8 T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. This is the first description of a post-translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8 T cell immune response. The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics.
结核分枝杆菌（Mtb）感染仍然是一个全球性的健康问题，Mtb 是导致结核病的细菌。经典和非经典受限细胞毒性 CD8 T 细胞对于控制 Mtb 感染都很重要。我们和其他人已经证明，非经典 MHC I 分子 HLA-E 可以将病原体衍生的肽呈递给 CD8 T 细胞。在本手稿中，我们鉴定了从潜伏性 Mtb 感染个体中分离出的 HLA-E 限制性 CD8 T 细胞克隆所识别的抗原，该抗原是 Mtb 蛋白 MPT32 的一个肽段。CD8 T 细胞克隆的识别需要由 Rv1002c 基因编码的甘露糖基转移酶对 MPT32 的 N 端 O-链接甘露糖基化。这是首次描述在 HLA-E 特异性 CD8 T 细胞免疫应答中呈递的翻译后修饰的 Mtb 衍生蛋白抗原。针对独特的分枝杆菌修饰的免疫反应的鉴定是新颖的，可能对疫苗和诊断的开发具有实际影响。
