Mechanisms Of Humoral Evasion

体液逃避的机制

• 批准号: 8336380
• 负责人: Peter D Kwong
• 金额: $ 83.55万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336380
• 关键词: Antibodies; Architecture; Binding; Binding Sites; Goals; HIV Envelope Protein gp120; HIV-1; Immune; Immune response; Infection; Masks; Methods; Polysaccharides; Site; Structure; Vaccines; Virus; base; conformational conversion; design; response

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.

HIV-1包膜包含体液免疫防御的多重重叠（和冗余）机制。 这些包括聚糖屏蔽，构象遮罩和具有可变环的免疫主导诱饵。 尽管经过广泛的探索，但其中许多机制仍然仅部分理解。 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结合位置如何使用构象掩蔽和聚糖屏蔽层隐藏CD4结合的保守位点，从大多数CD4结合位置定向的抗体中隐藏。 我们还研究了信封体系结构如何为构象移动性提供。 HIV-1 GP120内部域中的这些构象层调节GP41相互作用和CD4触发的构象转变。