具有高特异性的先天受体对HLA类I-复合物的高特异性
Malcolm J W Sim1, Paul Brennan1, Katherine L Wahl1
1Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
Science immunology
|September 8, 2023
概括
杀手细胞免疫球蛋白类受体 (KIR) 与HLA类I相互作用. 这项研究揭示了KIR-HLA相互作用的特点,影响疾病中的NK细胞反应.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 杀手细胞免疫球蛋白类受体 (KIRs) 和它们的HLA类I连接体与各种人类疾病有遗传联系.
- 确切的机制和抑制与激活KIR在NK细胞反应中的作用仍然不完全理解.
- 众所周知,KIR-HLA相互作用是依赖的,这表明免疫组起着至关重要的作用.
研究的目的:
- 系统地确定与四个HLA-C配体结合的五个KIR的特异性.
- 阐明特定的KIR-HLA-相互作用对NK细胞功能的贡献.
- 了解HLA-I对的呈现如何影响疾病背景下的NK细胞识别.
主要方法:
- 对特定的KIR-HLA-相互作用进行了超过3500次系统选.
- 评估了抑制性KIR2DL1,KIR2DL2,KIR2DL3和激活性KIR2DS1,KIR2DS4.4的结合亲缘关系和特异性.
- 对HLA-C复合物的KIR识别进行分析的序列依赖性.
主要成果:
- 抑制性KIR2DL1显示了广泛的,异性结合,约60%的测试HLA-复合体.
- 其他KIRs,包括KIR2DL2,KIR2DL3,KIR2DS1和KIR2DS4,表现出更受限制的结合,识别10%至1%的复合物.
- 激活KIR2DS1显示出对HLA-C的高结合亲和力和显著的序列特异性,与此前的描述相反.
结论:
- NK细胞受体表现出MHC受限的识别,挑战了以前的假设.
- 由HLA-I呈现的免疫组显著塑造NK细胞的反应.
- 这些发现提供了关于KIR-HLA与疾病和感染结果的关联的见解.
相关概念视频
Antigens Involved in Adaptive Immunity
536
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...
536
Antigen Processing Pathways
1.1K
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...
1.1K
Diversity of Antigen Receptors
627
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...
627
Cells of the Innate Immune Response
1.7K
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
1.7K
T Cell Activation and Clonal Selection
801
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...
801
Opioid Receptors: Overview
995
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
995


