Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype
Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype
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DOI：
10.1073/pnas.0707570104
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发表时间：
2007-10-09
影响因子：
11.1
通讯作者：
Pantaleo, Giuseppe
中科院分区：
文献类型：
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作者：
Harari, Alexandre;Cellerai, Cristina;Pantaleo, Giuseppe
我们研究了128名受试者对HIV-1、细胞负性病毒、Epstein-Barr病毒和流感的CD8 T细胞反应，证明多功能CD8 T细胞反应，包括IL-2的产生和抗原特异性的增殖，主要由受HLA-B等位基因限制的病毒表位驱动。有趣的是，这些保护性的CD8 T细胞配备了针对同源病毒表位的低亲和力T细胞受体(TCR)。相反，人类白细胞抗原限制性表位主要与“唯一效应者”干扰素-γ的分泌有关，具有细胞毒性，缺乏IL-2的产生和抗原特异性的增殖。这些CD8 T细胞配备了高亲和力的TCR，并表达更高水平的T细胞耗竭标记PD-1。因此，CD8 T细胞反应的功能特征受到多功能T细胞反应刺激程度的强烈影响(主要受人类白细胞抗原B的限制)，而不是仅受效应者的刺激(受人类白细胞抗原A的限制)。这些结果为观察到的人类白细胞抗原B在HIV-1感染中的保护作用提供了理论基础，并为TCR亲和力、PD-1表达和CD8T细胞功能谱之间的关系提供了新的见解。
We studied CD8 T cell responses against HIV-1, cytornegalovirus, Epstein-Barr virus, and influenza in 128 subjects and demonstrate that polyfunctional CD8 T cell responses, also including IL-2 production and Ag-specific proliferation, are predominantly driven by virus epitopes restricted by HLA-B alleles. Interestingly, these protective CD8 T cells are equipped with low-avidity T cell receptors (TCRs) for the cognate virus epitope. Conversely, HLA-Arestricted epitopes are mostly associated with "only effector" IFN-gamma-secreting, with cytotoxicity, and with the lack of IL-2 production and Ag-specific proliferation. These CD8 T cells are equipped with high-avidity TCR and express higher levels of the T cell exhaustion marker PD-1. Thus, the functional profile of the CD8 T cell response is strongly influenced by the extent to which there is stimulation of polyfunctional (predominantly restricted by HLA-B) versus only effector (restricted by HLA-A) T cell responses. These results provide the rationale for the observed protective role of HLA-B in HIV-1-infection and new insights into the relationship between TCR avidity, PD-1 expression, and the functional profile of CD8 T cells.