Mechanisms Of Humoral Evasion

HIV-1包膜包含多重重叠（和冗余）的体液免疫防御机制。 这些包括聚糖屏蔽、构象掩蔽和具有可变环的免疫显性诱饵。 尽管已经广泛探索，但其中许多机制仍然只是部分了解。 我们正在使用基于结构的方法来进一步定义它们。 特别是，我们研究了CD4结合位点如何使用构象掩蔽和聚糖屏蔽来隐藏大多数CD4结合位点定向抗体的CD4结合保守位点。 我们还研究了包膜结构如何提供构象移动性。 HIV-1 gp120内部结构域中的这些构象层调节gp41相互作用和CD4触发的构象转变。

The HIV-1 envelope contains multiply overlapping (and redundant) mechanisms of humoral immune defence. These including glycan shielding, conformational masking, and immunodominant decoys with variable loops. Although explored extensively, many of these mechanisms are still only partially understood. We are using structure-based methods to define them further. In particular, we have investigated how the CD4-binding-site uses conformational masking and glycan shielding to hide the conserved site of CD4 binding from most CD4-binding-site-directed antibodies. We have also investigated how the envelope architecture provides for conformational mobility. These conformational layers in the HIV-1 gp120 inner domain regulate gp41 interactions and CD4-triggered conformational transitions.