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Antigen presentation and the ubiquitin-proteasome system in host-pathogen interactions
Joana Loureiro1, Hidde L Ploegh
1Whitehead Institute, 9 Cambridge Center, Cambridge, Massachusetts, USA.
Advances in Immunology
|December 6, 2006
Summary
Pathogens manipulate host immune systems by targeting major histocompatibility complex (MHC) antigen presentation and the ubiquitin-proteasome system. Viral and bacterial strategies, like human cytomegalovirus (HCMV) immunoevasins, disrupt these pathways for immune evasion.
Area of Science:
- Molecular Biology
- Immunology
- Virology
- Microbiology
Background:
- Viruses and bacteria evolve rapidly, presenting constant challenges to host immune systems.
- Pathogens often evade or manipulate host immune responses, including antigen presentation.
- The ubiquitin-proteasome system is crucial for protein degradation and immune surveillance.
Purpose of the Study:
- To explore how viral and bacterial pathogens manipulate major histocompatibility complex (MHC) antigen presentation pathways.
- To investigate the role of the ubiquitin (Ub)-proteasome system in host-pathogen interactions.
- To detail specific mechanisms used by pathogens, such as human cytomegalovirus (HCMV) immunoevasins, to subvert immune detection.
Main Methods:
- Review and analysis of existing literature on pathogen manipulation of MHC class I and II antigen presentation.
- Focus on the mechanisms of ER-associated degradation (ERAD) employed by HCMV immunoevasins US2 and US11.
- Examination of pathogen interference with the Ub-proteasome system and deubiquitinating enzymes (DUBs).
Main Results:
- HCMV immunoevasins US2 and US11 catalyze ER dislocation of MHC class I heavy chains, leading to proteasomal degradation and immune evasion.
- Comparison of distinct ER dislocation pathways used by HCMV and murine herpes virus (MHV)-68.
- Pathogens extensively utilize and manipulate the Ub-proteasome system for various functions, including immune modulation, viral budding, and programmed cell death.
Conclusions:
- Pathogen exploitation of ER dislocation pathways offers insights into cellular ER quality control.
- Manipulation of the Ub-proteasome system is a central strategy for pathogens to overcome host defenses.
- Pathogen-encoded DUBs represent a novel area for modulating host-pathogen interactions.
Related Concept Videos
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...
01:13The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
02:18The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
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...
01:31Defense Against Bacterial Pathogens
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...