The structural basis of T cell activation by superantigens
1Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville 20850, USA.
Annual Review of Immunology
|June 8, 1999
Summary
Superantigens (SAGs) activate T cells by binding to T cell receptors (TCRs) and MHC class II molecules. Structural studies reveal how SAGs bypass normal T cell activation, leading to polyclonal T cell responses.
Area of Science:
- Immunology
- Structural Biology
- Microbial Pathogenesis
Background:
- Superantigens (SAGs) are potent bacterial or viral proteins that non-specifically activate T cells.
- T cell activation by SAGs involves simultaneous binding to the T cell receptor (TCR) Vβ domain and MHC class II molecules.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying T cell activation by superantigens.
- To understand how SAGs interact with TCR and MHC class II molecules at a structural level.
Main Methods:
- X-ray crystallography of bacterial SAGs, MHC class II molecules, and TCR beta chain complexes.
- Analysis of structural data to understand binding interactions and specificity.
Main Results:
- Detailed three-dimensional structures of SAG-MHC-TCR complexes were determined.
- Mechanisms by which SAGs circumvent normal peptide-MHC-mediated T cell activation were revealed.
- Insights into SAG specificity for TCR Vβ chains and the influence of the TCR α chain were gained.
Conclusions:
- Structural insights explain polyclonal T cell activation by SAGs.
- Understanding SAG-TCR/MHC interactions facilitates the design of SAG variants for research tools.
Related Concept Videos
01:26Antigens Involved in Adaptive Immunity
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 reactivity.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
01:28Diversity of Antigen Receptors
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...
01:22Antigen Presenting Cells
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...
01:31Antigen Processing Pathways
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...
01:22T 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...
Naive T cells that have not yet encountered an antigen express two primary CD...
01:24B 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...
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...