Related Experiment Video
Updated: Jun 6, 2026
08:09
Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes
Jan H Kessler1, Selina Khan, Ulrike Seifert
1Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. j.h.kessler@amc.uva.nl
Nature Immunology
|December 15, 2010
Summary
Cytotoxic T lymphocyte (CTL) epitope generation involves nardilysin and thimet oligopeptidase (TOP) alongside the proteasome. These enzymes broaden the peptide repertoire, enhancing immune defense against cancer and pathogens.
Area of Science:
- Immunology
- Molecular Biology
- Proteasome Biology
Background:
- Cytotoxic T lymphocytes (CTLs) are crucial for adaptive immunity, recognizing peptide antigens presented by HLA class I molecules.
- The proteasome is traditionally considered the primary enzyme responsible for generating the C-terminal ends of CTL epitopes.
- Understanding the full enzymatic machinery for antigen processing is vital for cancer immunotherapy and infectious disease research.
Purpose of the Study:
- To investigate the role of cytosolic endopeptidases, specifically nardilysin and thimet oligopeptidase (TOP), in the generation of CTL epitopes.
- To determine how nardilysin and TOP complement proteasome activity in antigen processing.
- To elucidate the contribution of these enzymes to the repertoire of antigenic peptides presented to CTLs.
Main Methods:
- Proteasome activity assays.
- Analysis of CTL epitope generation using nardilysin and TOP.
- Mass spectrometry-based peptidome profiling.
- Functional validation of epitopes derived from tumor antigens (PRAME, MART-1) and viral proteins (EBNA3C).
Main Results:
- Nardilysin and TOP were found to complement proteasome activity in CTL epitope generation.
- Both enzymes, individually or together, were essential for producing specific CTL epitopes from PRAME, EBNA3C, and MART-1.
- Thimet oligopeptidase (TOP) acted as a C-terminal trimming peptidase, while nardilysin contributed to both C-terminal and N-terminal processing.
- The combined action of these enzymes significantly broadens the repertoire of antigenic peptides.
Conclusions:
- Nardilysin and TOP play significant roles in antigen processing and CTL epitope generation, expanding beyond the known function of the proteasome.
- These enzymes are critical for generating a diverse range of antigenic peptides, thereby enhancing immune surveillance.
- Targeting nardilysin and TOP could represent a novel strategy to bolster immune responses against cancer and intracellular pathogens.
Related Concept Videos
01:27Cytotoxic 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...
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...
01:31Antigen 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...
01:26Antigens 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.
01:22Antigen 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...
01:29Immune Response Against Viral Pathogens
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:28Cells of the Innate Immune Response
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...