Ranasinghe Srinika, Lamothe Pedro A, Soghoian Damien Z, Kazer Samuel W, Cole Michael B, Shalek Alex K, Yosef Nir, Jones R Brad, Donaghey Faith, Nwonu Chioma, Jani Priya, Clayton Gina M, Crawford Frances, White Janice, Montoya Alana, Power Karen, Allen Todd M, Streeck Hendrik, Kaufmann Daniel E, Picker Louis J, Kappler John W, Walker Bruce D
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Immunity. 2016 Oct 18;45(4):917-930. doi: 10.1016/j.immuni.2016.09.015.
CD8 T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8 T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8 T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8 T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8 T cell responses can exist in a chronic human viral infection, and may contribute to immune control.
CD8 T细胞对病毒感染细胞的识别通常受主要组织相容性复合体（MHC）I类分子限制，不过在CD4缺陷小鼠以及一项使用重组巨细胞病毒载体的猕猴SIV疫苗试验中，也报道了罕见的MHC II类分子限制的例子。在此，我们证明在一小部分HIV感染个体中存在具有抗病毒特性的人类白细胞抗原（HLA）II类分子限制的CD8 T细胞应答。在这些个体中，T细胞受体β（TCRβ）分析显示，II类分子限制的CD8 T细胞发生了克隆扩增，并介导了对HIV感染细胞的杀伤。在一个病例中，这些细胞占循环CD8 T细胞的12%，TCRα分析显示有两条不同的共表达TCRα链，其中只有一条参与II类HLA-肽复合物的结合。这些数据表明，II类分子限制的CD8 T细胞应答可存在于慢性人类病毒感染中，并可能有助于免疫控制。
