本地和人工抗体景观的生物物理地图绘制量化了抗体开发能力的可塑性
Habib Bashour1,2, Eva Smorodina3, Matteo Pariset4
1Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway. habib.bashour@medisin.uio.no.
Communications biology
|July 31, 2024
概括
了解抗体开发能力是设计有效治疗方法的关键. 这项研究绘制了自然和人工抗体开发能力的地图,揭示了人工抗体占据了自然抗体多样性中的子空间.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 计算生物学 计算生物学
背景情况:
- 治疗单克隆抗体 (mAb) 设计需要优化"可开发性",这是对发展至关重要的物理化学性质的衡量标准.
- 自然抗体提供了洞察力,但它们的发育性参数 (DP) 塑性和与工程抗体的关系仍然不太清楚.
- 这种知识缺口限制了对抗体开发能力概况的全面映射.
研究的目的:
- 为了绘制自然和人为工程抗体的可开发性景观.
- 量化抗体开发能力参数的可塑性 (冗余性,可预测性,灵敏性).
- 了解工程抗体开发能力如何与自然抗体景观相关.
主要方法:
- 计算了40个基于序列和46个基于结构的可开发性参数 (DPs),用于超过200万个原生和人造单链抗体序列.
- 分析了DP冗余性,对氨基酸替代物的敏感性和形状变异性.
- 利用机器学习进行序列和结构DP可预测性评估.
主要成果:
- 基于结构的DP显示的冗余性低于基于序列的DP.
- 序列DP灵敏度因抗体区域和DP而异;结构DP值在整个构造组合中波动.
- 序列DP比基于结构的DP更可预测,这表明序列设计空间受限.
- 人造抗体在自然抗体开发能力和序列格局的子空间内被发现.
结论:
- 这项研究量化了抗体开发可塑性,为治疗mAb设计提供了基础资源.
- 工程抗体只能探索自然抗体开发空间的一个子集.
- 这些发现有助于更明智的多参数优化,以实现有效的治疗 mAb 开发.
相关概念视频
01:10Antibody Structure
59.8K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
59.8K
01:25Antibody Structure and Classes
861
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
861
01:28Diversity of Antigen Receptors
554
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
554