There are two primary classes of major histocompatibility complex (MHC) molecules, class I and MHC class II. The major histocompatibility complex ( MHC) is a large genomic region or Gene family found in most Vertebrates It is the most gene-dense region MHC ( Major histocompatibility complex) Class II molecules are found only on a few specialized cell types including Macrophages Dendritic cells and MHC class I molecules are found on almost every nucleated cell of the body. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called the cytosolic or endogenous pathway.
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Structure
MHC class I molecules are heterodimers, consisting of a single transmembrane polypeptide chain (the α-chain) and a β2 microglobulin (which is encoded elsewhere, not in the MHC). A dimer is a Chemical or Biological entity consisting of two subunits called Monomers which are held together by either Intramolecular forces A transmembrane protein is a Protein that spans the entire Biological membrane. β2 microglobulin also known as B2M is a component of MHC class I molecules which are present on almost all cells of the body ( Red blood cells The α chain has three polymorphic domains, α1, α2, α3. Between α1 and α2 is the peptide-binding groove which binds peptides derived from cytosolic proteins. The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. The groove consists of eight β-pleated sheets on the bottom and two α helices making up sides. The peptide in the groove remains bound for the life of the class I molecule, and is typically 8-9 amino acids in length.
Production
The peptides are mainly generated in the cytosol by the proteasome. The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. Proteasomes are large Protein complexes inside all Eukaryotes and Archaea, as well as in some Bacteria. The proteasome is a macromolecule that consists of 28 subunits, of which half of them contain proteolytic activity. Proteolysis is the directed degradation ( digestion) of Proteins by cellular Enzymes called Proteases or by intramolecular digestion The proteasome degrades intracellular proteins into small peptides that are then released into the cytosol. The peptides have to be translocated from the cytosol into the endoplasmic reticulum (ER) to meet the MHC class I molecule, whose peptide-binding site is in the lumen of the ER. The endoplasmic reticulum (Greek endo = "within" (prefix plásma = "formed entity" Latin reticulum = "little net" or ER, is an Organelle
Translocation
The peptide translocation from the cytosol into the lumen of the ER is accomplished by the transporter associated with antigen processing (TAP). Transporter associated with antigen processing ( TAP) is a member of the ATP-binding-cassette transporter family. TAP is a member of the ABC transporter family and is a heterodimeric multimembrane-spanning polypeptide consisting of TAP1 and TAP2. ATP-binding cassette transporters ( ABC-transporter) are members of a superfamily that is one of the largest and most ancient families with representatives in all extant The two subunits form a peptide binding site and two ATP binding sites that face the lumen of the cytosol. TAP binds peptides on the cytoplasmic site and translocates them under ATP consumption into the lumen of the ER. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy The MHC class I molecule is then in turn loaded with peptides in the lumen of the ER. The peptide-loading process involves several other molecules that form a large multimeric complex consisting of TAP, tapasin, calreticulin, calnexin, and ERP57. TAP binding protein (tapasin, also known as TAPBP, is encoded for by a human Gene. Calreticulin is a multifunctional Protein that binds Ca2+ Ions (a Second messenger Molecule in Signal transduction Calnexin (CNX is a 90kDa Integral protein of the Endoplasmic reticulum (ER Protein disulfide isomerase family A member 3 ( PDIA3) also known as glucose-regulated protein 58-kD ( GRP58) is an Isomerase Enzyme
Once the peptide is loaded onto the MHC class I molecule, it leaves the ER through the secretory pathway to reach the cell surface. The secretory pathway is a series of steps a cell uses to move Proteins out of the cell a process known as secretion. The transport of the MHC class I molecules through the secretory pathway involves several posttranslational modifications of the MHC molecule. Posttranslational modification (PTM is the chemical modification of a Protein after its translation. Some of the posttranslational modifications occur in the ER and involve change to the N-glycan regions of the protein, followed by extensive changes to the N-glycans in the Golgi apparatus. The Golgi apparatus (also called the The N-glycans mature fully before they reach the cell surface.
Peptide removal
Peptides that fail to bind MHC class I molecules in the lumen of the endoplasmic reticulum are removed from the ER via the sec61 channel into the cytosol, where they might undergo further trimming in size, and might be translocated by TAP back into ER for binding to an MHC class I molecule. Sec61 is an Endoplasmic reticulum (ER membrane protein translocator (aka Translocon)
Effect of viruses
MHC class I molecules are loaded with proteins generated in the cytosol. As viruses infect a cell by entering its cytoplasm, this cytosolic, MHC class I-dependent pathway of antigen presentation is the primary way for a virus-infected cell to signal T cells. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. MHC class I molecules generally interact exclusively with CD8+ ("cytotoxic") T cells (CTLs). A cytotoxic T cell (also known as TC, CTL T-Killer cell cytolytic T cell CD8+ T-cells or killer T cell) belongs to a sub-group of T lymphocytes The fate of the virus-infected cell is almost always apoptosis initiated by the CTL, effectively reducing the risk of infecting neighboring cells.
Genes and isotypes
Additional images
 TCR-MHC bindings |
External links
HLA-A are a group of Human leukocyte antigens (HLA that are encoded by the HLA-A locus on human chromosome 6p HLA-B ( major histocompatibility complex class I B) is a Human Gene that provides instructions for making a Protein that plays a critical Serotype Disease associations Spondylarthropathies The relationship between HLA-B27 and many diseases has not yet been fully elucidated HLA-C belongs to the MHC (human = HLA class I heavy chain receptors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and booksDapyx Software network: MP3 Explorer | Ebook Manager | Zenithic