Systems Biology
The major histocompatibility complex (MHC) is a group of highly polygenic and polymorphic genes that code for MHC molecules. These glycoproteins are found on the surface of cells and present self and foreign antigens or peptides to T-cells in order to coordinate an appropriate immune response. In humans, this complex is also called the human leukocyte antigen (HLA) system. The MHC includes MHC class I molecules and MHC class II molecules.
MHC class I molecules are found on all nucleated cells and bind endogenous peptides in the rough endoplasmic reticulum (ER). They then present these peptides at the cell surface to be recognized by cytotoxic T-cells and natural killer cells. On the other hand, MHC class II molecules are found only on antigen-presenting cells (APCs), such as macrophages, dendritic cells, and B-cells. These molecules bind peptide fragments from exogenous pathogens in the organelle that forms when the endosome and the phagolysosome fuse. The peptides are then presented at the cell surface to be recognized by helper T-cells.
Lesson Outline
<ul> <li>Major histocompatibility complex (MHC) <ul> <li>Group of highly polygenic and polymorphic genes coding for MHC molecules</li> <li>Also known as human leukocyte antigen (HLA) system in humans</li> <li>Glycoproteins found on the surface of cells</li> <li>Present self and foreign antigens or peptides to T-cells</li> <li>MHC class I molecules and MHC class II molecules</li> </ul> </li> <li>MHC class I molecules <ul> <li>Found on all nucleated cells</li> <li>Bind endogenous peptides in the rough endoplasmic reticulum (ER)</li> <li>Present peptides at the cell surface for recognition by cytotoxic T-cells and natural killer cells</li> </ul> </li> <li>MHC class II molecules <ul> <li>Found only on antigen-presenting cells (APCs), such as macrophages, dendritic cells, and B-cells</li> <li>Bind peptide fragments from exogenous pathogens</li> <li>Peptides are bound in the organelle that forms when the endosome and the phagolysosome fuse</li> <li>Present peptides at the cell surface for recognition by helper T-cells</li> </ul> </li> </ul>
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FAQs
MHC class I molecules are found on the surface of almost all nucleated cells and are responsible for presenting endogenous antigens (derived from inside the cell) to cytotoxic T-cells (CD8 T-cells) and natural killer (NK) cells. MHC class II molecules are primarily found on the surface of antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B-cells. These molecules present exogenous antigens (derived from outside the cell) to helper T-cells (CD4 T-cells). Additionally, MHC class I molecules present peptides from the endogenous pathway, while MHC class II molecules present peptides from the exogenous pathway.
APCs, such as dendritic cells, macrophages, and B-cells, play a crucial role in the initiation of the immune response. They work as a bridge between the innate and adaptive immune systems. Upon encountering foreign antigens, APCs capture, process, and present the antigenic peptides on their MHC class II molecules. The APCs then migrate to the lymphoid tissues, where they present the peptides to helper T-cells (CD4 T-cells). This interaction activates the helper T-cells, which subsequently coordinate different aspects of the immune response, including the activation of cytotoxic T-cells and B-cells to eliminate infected cells and produce antibodies, respectively.
MHC class I molecules play a critical role in the immune response against viral infections. When a cell is infected by a pathogen, it produces foreign proteins that are broken down into small peptides within the cell. These peptides are then loaded onto the MHC class I molecules and transported to the cell surface. Cytotoxic T-cells (CD8 T-cells) recognize the MHC class I-peptide complex, which activates them. Once activated, the cytotoxic T-cells can then release molecules that induce apoptosis (cell death) in the infected cell, effectively eliminating the pathogen and preventing further spread of the infection.
MHC class I and class II molecules contribute significantly to the immune system's ability to discriminate between self and foreign antigens. Each individual has a unique set of MHC molecules, which present self-antigens derived from normal cellular proteins. During T-cell development, T-cells that strongly recognize self-antigens are eliminated in a process called negative selection, ensuring that the mature T-cells are less likely to attack the body's own cells. When foreign antigens (e.g., from pathogens) are presented by MHC molecules, T-cells can recognize them as non-self, leading to the activation of immune responses against the foreign antigens.
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