Attenuation of CD4+ T-cell function by human adenovirus type 35 is mediated by the knob protein
Attenuation of CD4+ T-cell function by human adenovirus type 35 is mediated by the knob protein
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DOI：
10.1099/vir.0.039222-0
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发表时间：
2012-06-01
影响因子：
3.8
通讯作者：
Lore, Karin
中科院分区：
文献类型：
--
作者：
Adams, William C.;Berenson, Ronald J.;Lore, Karin
补体调节蛋白CD 46是人腺病毒35型（HAdV-35）的主要受体，可调节人免疫细胞活化。CD 4（+）T细胞对于启动和维持由感染或疫苗接种引起的适应性免疫至关重要。先前报道HAdV-35可以结合这些细胞并抑制它们的活化。本文报道的数据表明，重组三聚体HAdV-35球蛋白单独可以诱导CD 46受体下调，并抑制白细胞介素-2的产生和体外人CD 4（+）T细胞的增殖，类似于特异性针对HAdV-35球结合的CD 46区域的mAb。与野生型旋钮相比，突变的旋钮蛋白与CD 46的亲和力增加，导致等效的效果。与此相反，CD 46结合缺陷突变结蛋白不抑制T细胞活化。因此，HAdV-35减弱人CD 4（+）T细胞活化的能力主要取决于与CD 46的结相互作用，并且可以独立于感染而发生。
The complement-regulatory protein CD46 is the primary receptor for human adenovirus type 35 (HAdV-35) and can regulate human immune-cell activation. CD4(+) T-cells are critical for initiating and maintaining adaptive immunity elicited by infection or vaccination. It was reported previously that HAdV-35 can bind these cells and suppress their activation. The data reported here demonstrate that recombinant trimeric HAdV-35 knob proteins alone can induce CD46 receptor downregulation and inhibit interleukin-2 production and proliferation of human CD4(+) T-cells in vitro similarly to mAbs specific to the CD46 region bound by HAdV-35 knobs. A mutant knob protein with increased affinity for CD46 compared with the wild-type knob caused equivalent effects. In contrast, a CD46-binding-deficient mutant knob protein did not inhibit T-cell activation. Thus, the capacity of HAdV-35 to attenuate human CD4(+) T-cell activation depends predominantly on knob interactions with CD46 and can occur independently of infection.