Structural model of HLA-DR1 restricted T cell antigen recognition
J B Rothbard1, R I Lechler, K Howland
1Laboratory of Molecular Immunology, Imperial Cancer Research Fund, London, England.
Cell
|February 26, 1988
Summary
Researchers identified two key influenza T cell determinants, one in hemagglutinin and one in matrix protein (M1). These findings reveal a specific helical pattern crucial for DR1-restricted T cell recognition in influenza and other allergies.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Helper T cells play a critical role in adaptive immunity, recognizing peptide antigens presented by MHC class II molecules.
- Influenza virus proteins contain epitopes that elicit T cell responses, contributing to viral clearance and immune memory.
- Human Leukocyte Antigen (HLA) class II alleles, such as HLA-DR1, restrict T cell recognition of specific peptide sequences.
Purpose of the Study:
- To identify and characterize human helper T cell determinants within influenza virus proteins.
- To investigate the structural basis for DR1 restriction of T cell recognition of influenza-derived peptides.
- To explore the potential for a generalizable motif in DR1-restricted T cell epitope recognition.
Main Methods:
- Transfected L cells were used to present antigen and assess DR1 restriction of T cell determinants from influenza hemagglutinin and matrix protein (M1).
- Peptide sequence comparison and analysis of amino acid interactions with DR1 and T cell receptors were performed.
- Hybrid peptides were synthesized and tested for recognition by T cell clones.
- Response of DR1 individuals to a ragweed peptide containing the identified motif was evaluated.
Main Results:
- Two human helper T cell determinants were identified in influenza hemagglutinin and matrix protein (M1).
- Both determinants were shown to be DR1 restricted.
- A shared sequence pattern, likely adopting a helical conformation, was proposed to explain DR1 specificity.
- Hybrid peptides confirmed the interaction model, and a ragweed peptide with the motif elicited a response in DR1 individuals.
Conclusions:
- A specific sequence motif, potentially helical, underlies DR1-restricted T cell recognition of influenza epitopes.
- This motif may be a general feature of DR1-restricted T cell determinants, extending beyond influenza.
- Understanding these determinants can inform vaccine design and immunotherapy strategies for infectious diseases and allergies.
More Related Videos
Related Concept Videos
01:40Cell-mediated Immune Responses
Overview
01:20Special Features of Adaptive Immunity
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,...
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...
01:31Antigen 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...