一种结构导向的方法来预测MHC-I对T细胞受体对公共抗原的限制
bioRxiv : the preprint server for biology
|June 19, 2024
概括
本研究根据它们的相互作用表面将人类白细胞抗原 (HLA) 的全型分为T细胞交叉反应组 (T-CREGs). 这种分类有助于理解T细胞受体 (TCR) 结合和开发新的免疫疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 由人类白细胞抗原 (HLA) I 类蛋白质呈现的是T细胞受体 (TCR) 和TCR模仿抗体 (TMA) 疗法的关键生物标志物.
- TCRs和TMAs表现出有限的识别,与有限的HLA全型呈现的特定结合.
研究的目的:
- 分析TCR:-HLA (pHLA) 复杂结构以确定TCR接触残留物.
- 根据表面相互作用特征将常见的HLA全型分为T细胞交叉反应性组 (T-CREGs).
- 为解决MHC-I限制提供见解,并指导免疫疗法的开发.
主要方法:
- 来自蛋白质数据库 (PDB) 的96个TCR:pHLA复杂结构的分析.
- 在TCR:pHLA接口内识别TCR接触残留物.
- 用结构表面特征将148种常见的HLA类型分类为T-CREG.
主要成果:
- 定义的TCR接触残留物参与HLA-的识别.
- 建立了148种HLA全型的T-CREG分类系统.
- 证明HLA全型可以根据它们与TCR结合相关的相互作用表面特征进行分组.
结论:
- T-CREG分类为理解TCR特异性和MHC-I限制提供了一个框架.
- 这种分类在扩展现有的基于TCR的疗法和设计新型免疫疗法策略方面具有实际应用.
- 这些发现有助于为癌症免疫疗法选择最佳标.
相关概念视频
Antigens Involved in Adaptive Immunity
483
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
483
Antigen Processing Pathways
989
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
MHC Class I: Presenting Endogenous...
989
Diversity of Antigen Receptors
566
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...
566
T Cell Activation and Clonal Selection
701
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
701


