欠陥T細胞受容体シグナル伝達とVaV欠乏性CD4+CD8+シモサイトの陽性選択

K D Fischer¹, A Zmuldzinas, S Gardner

¹Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Nature

|March 30, 1995

まとめ

タンパク質Vavは,Tリンパ球とBリンパ球の生成に不可欠です. Vav欠乏はリンパ球のシグナル伝達と成熟を阻害しますが,T細胞発達の過程で系統の結合を阻害しません.

科学分野:

免疫学免疫学とは
分子生物学は分子生物学である.
細胞生物学細胞生物学

背景:

リンパ球の発達には,増殖と選択の正確な規制が必要です.
抗原受容体の関与は,Vav.のような主要なタンパク質のチロシンリン酸化を含むシグナリングカスケードを開始します.

研究の目的:

TおよびBリンパ球の発達と抗原受容体シグナル伝達におけるVavタンパク質の役割を調査する.
陽性選択中のT細胞の成熟と系統のコミットメントにおけるVavの機能を決定する.

主な方法:

胚性幹細胞のvav-/-を用いたRAG-2ブラストシストコンプリメンテーションアッセイを用いた.
Vav欠乏細胞におけるTリンパ球抗原受容体シグナリングを分析した.
Vav欠乏性T細胞におけるT細胞の成熟とCD4/CD8系統へのコミットメントを調べた.

主要な成果:

Vav欠乏症は,未成熟および成熟したTおよびBリンパ球の生産を制限しました.
Vav欠乏性Tリンパ球は,抗原受容体シグナル伝達が著しく低下したことを示した.
Vav依存の経路はT細胞の成熟を調節するが,CD4/CD8系統へのコミットメントを調節しない.

結論:

Vavは,効率的なTおよびBリンパ球の発達と適切な抗原受容体シグナル伝達に不可欠です.
Vavは,T細胞受容体媒介の陽性選択によるT細胞成熟において重要な役割を果たします.

さらに関連する動画

10:10

Preparation and Applications of Organotypic Thymic Slice Cultures

Published on: August 6, 2016

08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

関連する概念動画

01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...

01:22

T Cell Activation and Clonal Selection

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...

01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...

01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...

01:24

B Cell Activation and Differentiation

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...

01:25

Immunodeficiency Diseases

Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency disorders...

関連する実験動画