公共 T 细胞克隆型在 HLA-B57:01/艾滋病毒患者中独立于病毒载量被选择。
Public T cell clonotypes are selected in HLA-B57:01/HIV patients independently of the viral load.
机构信息
Immunity and Infection Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Immunity and Infection Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
出版信息
Cell Rep. 2024 Aug 27;43(8):114555. doi: 10.1016/j.celrep.2024.114555. Epub 2024 Jul 30.
HIV controllers can control viral replication and remain healthy, but the mechanism behind this control is unknown. Despite human leukocyte antigen (HLA) diversity in the population, almost 50% of HIV controllers express the HLA-B57:01 molecule, which presents, among others, the Gag-derived epitope TW10. Given TW10's presentation in early infection, TW10-specific T cells could participate in the control of HIV. Here, we study the strength and functionality of TW10-specific T cells from HLA-B57:01/HIV controller and non-controller individuals. We determine the TW10-specific T cell receptor (TCR) repertoire, revealing a bias in TCR gene usage with the presence of a public TCR. We determine that the T cell response is polyfunctional regardless of the viral load, despite the low affinity of TW10-specific TCRs. We solve the crystal structure of HLA-B57:01-TW10 in complex with a TCR, providing the basis of recognition that underpins the strong TRBV5 bias observed in TW10-specific clonotypes.
HIV 控制器可以控制病毒复制并保持健康，但这种控制的机制尚不清楚。尽管人群中存在人类白细胞抗原（HLA）多样性，但近 50%的 HIV 控制器表达 HLA-B57:01 分子，该分子除其他外，还呈递源自 Gag 的表位 TW10。鉴于 TW10 在早期感染中的呈递，TW10 特异性 T 细胞可能参与 HIV 的控制。在这里，我们研究了来自 HLA-B57:01/HIV 控制器和非控制器个体的 TW10 特异性 T 细胞的强度和功能。我们确定了 TW10 特异性 T 细胞受体（TCR）库，揭示了 TCR 基因使用的偏向性，存在公共 TCR。我们确定无论病毒载量如何，T 细胞反应都是多功能的，尽管 TW10 特异性 TCR 的亲和力较低。我们解决了 HLA-B57:01-TW10 与 TCR 复合物的晶体结构，为识别提供了基础，这为观察到的 TW10 特异性克隆型中强烈的 TRBV5 偏向性提供了依据。
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