Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
ImmunoMod Consulting, Seattle, WA, USA.
J Gen Virol. 2012 Jun;93(Pt 6):1339-1344. doi: 10.1099/vir.0.039222-0. Epub 2012 Feb 22.
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.
补体调节蛋白 CD46 是人类腺病毒 35 型（HAdV-35）的主要受体，可调节人类免疫细胞的激活。CD4+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。先前有报道称，HAdV-35 可以结合这些细胞并抑制其激活。这里报告的数据表明，重组三聚体 HAdV-35 旋钮蛋白本身就可以诱导 CD46 受体下调，并抑制体外人类 CD4+T 细胞产生白细胞介素 2 和增殖，与针对 HAdV-35 旋钮结合的 CD46 区域的特异性 mAb 相似。与野生型旋钮相比，与 CD46 亲和力增加的突变旋钮蛋白引起等效的效果。相比之下，缺乏 CD46 结合能力的突变旋钮蛋白不会抑制 T 细胞激活。因此，HAdV-35 减弱人类 CD4+T 细胞激活的能力主要取决于旋钮与 CD46 的相互作用，并且可以独立于感染发生。
