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 Antigens
MHC class I molecules present endogenous antigens, which are antigens derived from proteins synthesized within the cell. These could be viral proteins, tumor antigens, or self-proteins that have undergone modifications.
In this pathway, intracellular proteins from abnormal or virus-infected cells are degraded by the proteasome, a cellular machinery responsible for protein degradation. The resulting peptide fragments are then transported into the endoplasmic reticulum, or ER, by the transporter associated with antigen processing (TAP). Inside the ER, these peptide fragments bind to newly synthesized MHC I molecules, forming an MHC I-peptide complex. This complex is transported to the cell surface via the Golgi apparatus and exocytosis.
MHC Class II: Presenting Exogenous Antigens
MHC class II molecules specialize in presenting exogenous antigens, which originate from extracellular sources such as bacteria or toxins. These antigens are engulfed by antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells.
The exogenous antigen presentation pathway is crucial for the immune response against pathogens outside cells. In this pathway, APCs ingest pathogens through phagocytosis, a process by which certain immune cells, such as macrophages, engulf and digest large particles or microbes. Once inside the APC, the pathogen is enclosed in a phagosome, which fuses with a lysosome to form a phagolysosome. Various enzymes break down the pathogen into smaller peptide fragments within this structure.
These peptide fragments are then loaded onto MHC II molecules within the APCs' endosomes or lysosomes to form an MHC II-peptide complex, which is transported to the cell surface.
The antigen-processing pathways break down antigens for presentation to lymphocytes.
The endogenous and exogenous pathways are the two main antigen-processing pathways.
The endogenous pathway involves MHC I molecules and processes antigens from within the cell, typically those produced by viruses and abnormal tumor proteins.
Within the cell, the proteasome degrades these intracellular antigenic proteins into peptide fragments.
These fragments bind to the newly synthesized MHC I molecules within the ER, creating MHC I-antigen complexes, which are then inserted into the cell membrane.
In contrast, antigen-presenting cells, such as the dendritic cells equipped with MHC II molecules, participate in the exogenous pathway.
These APCs ingest and enclose pathogens, such as bacteria and fungi, in phagosomes or endosomes that fuse with lysosomes.
Next, the pathogen is enzymatically degraded into smaller antigenic fragments.
Simultaneously, the ER secretes vesicles carrying MHC II molecules, which fuse with the vesicles carrying the antigen fragments.
The foreign peptides then bind MHC II to form the MHC II-peptide complex, which is then expressed on the cell membrane.
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