South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
Nat Med. 2023 Jan;29(1):258-269. doi: 10.1038/s41591-022-02110-9. Epub 2023 Jan 5.
Antigen-specific, MHC-restricted αβ T cells are necessary for protective immunity against Mycobacterium tuberculosis, but the ability to broadly study these responses has been limited. In the present study, we used single-cell and bulk T cell receptor (TCR) sequencing and the GLIPH2 algorithm to analyze M. tuberculosis-specific sequences in two longitudinal cohorts, comprising 166 individuals with M. tuberculosis infection who progressed to either tuberculosis (n = 48) or controlled infection (n = 118). We found 24 T cell groups with similar TCR-β sequences, predicted by GLIPH2 to have common TCR specificities, which were associated with control of infection (n = 17), and others that were associated with progression to disease (n = 7). Using a genome-wide M. tuberculosis antigen screen, we identified peptides targeted by T cell similarity groups enriched either in controllers or in progressors. We propose that antigens recognized by T cell similarity groups associated with control of infection can be considered as high-priority targets for future vaccine development.
针对结核分枝杆菌的保护性免疫需要抗原特异性、 MHC 限制性的 αβ T 细胞，但广泛研究这些反应的能力受到限制。在本研究中，我们使用单细胞和批量 T 细胞受体（TCR）测序和 GLIPH2 算法分析了两个纵向队列中的结核分枝杆菌特异性序列，该队列包括 166 名结核分枝杆菌感染患者，其中 48 名进展为结核病，118 名得到控制。我们发现了 24 个具有相似 TCR-β 序列的 T 细胞群，GLIPH2 预测它们具有共同的 TCR 特异性，与感染控制（n=17）相关，而其他与疾病进展（n=7）相关。使用全基因组结核分枝杆菌抗原筛选，我们鉴定了 T 细胞相似性群所识别的肽段，这些肽段在控制者或进展者中富集。我们提出，与感染控制相关的 T 细胞相似性群识别的抗原可以被认为是未来疫苗开发的高优先级目标。
