The HLA class I molecule is a heterodimeric membrane bound glycoproteins which is made up of a polymorphic α or heavy chain (43 kDa), encoded by genes within the MHC class I region on the short arm of chromosome 6 (6p21.3), in non covalent association with a non polymorphic β2 microglobulin (12 kDa) protein which is coded for on chromosome 15. The α-chain, which is made up of three extra cellular domains, α1, 2 and 3, a transmembrane region and a cytoplasmic chain, anchors the class I molecule to the cell membrane.
The class I molecule α3 domain and β2 microglobulin are proximal to the cell membrane. They have a folded structure which resembles that of the C domain of an immunoglobulin molecule. The α1 and α2 domains are distal to the cell membrane. They fold together into a structure consisting of a pair of anti-parallel α helix side walls flanking a floor of anti-parallel β pleated sheets. This creates a groove into which peptides can bind. Peptides bound by class I are typically of 8 – 10 amino acids in length and are bound through a series of hydrogen bonds and ionic interactions at each end of the peptide. The amino acids that line this peptide binding groove account for the most of the polymorphism of the HLA class I gene and have a direct impact on the nature of the peptide that can bind.
The main function of HLA class I molecules is to present intracellularly derived peptide to CD8+ cytotoxic T cells. The presentation of peptides from pathogen can lead to an immune response that results in the killing of the infected cell. HLA class I molecules are expressed on almost all nucleated cells, though the level of expression does vary between cells.
The HLA class II molecule is a heterodimeric membrane bound glycoprotein which is made up of two non-covalently associated polymorphic chains, α (34 kDa) and β (29 kDa). Both chains span the membrane. The α and β chains are both encoded by genes within the MHC class II region on the short arm of chromosome 6 (6p21.3). They both contribute two domains each, α1 and α2 and β1 and β2. The α2 and β2 domains are proximal to the cell membrane. They have a folded structure that resembles the C domain of an immunoglobulin molecule. The α1 and β1 domains are distal from the cell surface. They fold together into a structure consisting of a pair of anti-parallel α helix side walls flanking a floor of anti-parallel β pleated sheets. The α1 and β1 domains come together to form a groove which is open at both ends which allowing longer peptides to bind. The amino acids that line this peptide binding groove, mainly in the β chain but also in the α chain, account for most of the polymorphism of the HLA class II gene.
The main function of HLA class II molecules is to present extracellular derived peptide to CD4+ helper T cells. This elicits an immune response, including B cell activation for production of antibodies and cytotoxic T cell activation. HLA class II molecules are expressed mainly on cells of the immune system, though the level of expression on resting T cells is lower than on other cells.
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