激酶激活的B细胞受体促进了对质敏感自身免疫细胞中致病性T细胞的抗原呈现
Rasmus Iversen1,2, Julie Elisabeth Heggelund3,4, Saykat Das3,4
1Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. rasmus.iversen@medisin.uio.no.
Nature communications
|March 11, 2025
概括
在皮肤炎形炎 (DH) 中,对转质胺酶3 (TG3) 的自身抗体会促进T细胞的质呈现. 这发生在TG3特异性B细胞内部化TG3质复合体时,增强酶活性和T细胞激活.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 这是一种自身免疫力.
背景情况:
- 皮肤炎形 (DH) 是一种皮肤表现的乳病,其特点是对转谷氨酶3 (TG3) 的自身抗体.
- 通过TG3自身抗体对DH病原发生的贡献的确切机制仍然不完全理解.
研究的目的:
- 阐明TG3特异性B细胞激活DH中的质特异性T细胞的机制.
- 研究TG3自身抗体在调节TG3酶活性和抗原呈现中的作用.
主要方法:
- 对TG3-质复合物的B细胞受体 (BCR) 中介内部化进行分析.
- 使用X射线结晶学对TG3与IGHV2-5/IGKV4-1 Fab片段结合的结构研究.
- 对T细胞的TG3催化活性和质呈现的评估.
主要成果:
- 特定于TG3的B细胞通过BCR介导的TG3质复合物的内部化来激活特定于质的CD4+T细胞.
- 使用IGHV2-5/IGKV4-1基因段的刻板反TG3抗体增强了TG3的催化活性.
- 与TG3结合的抗体诱导了活性构造,增加了T细胞的质呈现.
- 晶体结构显示了抗体与催化核心域中的β-sheet结合.
结论:
- TG3 特定的 B 细胞作为 DH 中的质特异性 T 细胞的抗原呈现细胞.
- 该机制涉及抗体增强的TG3活性,导致质呈现增加.
- 这一发现为DH的发病过程提供了洞察力,并提出了潜在的治疗点.
- 在其他涉及自身反应性B细胞的自身免疫性疾病中,类似的机制可能是相关的.
相关概念视频
B Cell Activation and Differentiation
1.4K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.4K
Autoimmune Disorders
374
Autoimmune diseases are a group of disorders in which the body's immune system mistakenly attacks its own cells, tissues, and organs. This results from an overactive immune response against substances and tissues normally present in the body. Let's delve into the concept and mechanism of autoimmune diseases from an immune system point of view, explore different causes and examples of such diseases, and discuss potential solutions.
Concept and Mechanism of Autoimmune Diseases
The immune...
Concept and Mechanism of Autoimmune Diseases
The immune...
374
T Cell Activation and Clonal Selection
622
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...
622
Antigens Involved in Adaptive Immunity
434
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...
434
Special Features of Adaptive Immunity
707
The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
707
Antigen Presenting Cells
1.6K
The immune system is a complex network of cells and molecules that protects the body from foreign invaders. T cells, a type of white blood cell, play a crucial role in this process. They recognize and attack foreign substances, such as pathogens, that enter the body.
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
1.6K


