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HLA-A
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I transmembrane proteins. The others are HLA-B and HLA-C. The protein is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant HLA-A gene, and the β chain (β2-microglobulin) is an invariant β2 microglobulin molecule. The β2 microglobulin protein is encoded by the B2M gene, which is located at chromosome 15q21.1 in humans. MHC Class I molecules such as HLA-A are part of a process that presents short polypeptides to the immune system. These polypeptides are typically 7-11 amino acids in length and originate from proteins being expressed by the cell. There are two classes of polypeptide that can be presented by an HLA protein: those that are supposed to be expressed ...
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HLA-A Gene
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus (genetics), locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I transmembrane proteins. The others are HLA-B and HLA-C. The protein is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant #HLA-A gene, HLA-A gene, and the β chain (β2-microglobulin) is an invariant Beta-2 microglobulin, β2 microglobulin molecule. The β2 microglobulin protein is encoded by the B2M gene, which is located at chromosome 15q21.1 in humans. MHC Class I molecules such as HLA-A are part of a process that presents short polypeptides to the immune system. These polypeptides are typically 7-11 amino acids in length and originate from proteins being expressed by the cell. There are two classes of polypeptide that can be presented by an H ...
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History And Naming Of Human Leukocyte Antigens
Human leukocyte antigens (HLA) began as a list of antigens identified as a result of transplant rejection. The antigens were initially identified by categorizing and performing massive statistical analyses on interactions between blood types.Davis, Daniel M. The Compatibility Gene. How Our Bodies Fight Disease, Attract Others, and Define Our Selves. Oxford: Oxford UP, 2014. Print. This process is based upon the principle of serotypes. HLA are not typical antigens, like those found on surface of infectious agents. HLAs are ''allo''antigens, they vary from individual to individual as a result of genetic differences. An organ called the thymus is responsible for ensuring that any T-cells that attack self proteins are not allowed to live. In essence, every individual's immune system is tuned to the specific set of HLA and self proteins produced by that individual; where this goes awry is when tissues are transferred to another person. Since individuals almost always have different "ba ...
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Major Histocompatibility Complex
The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules. This locus got its name because it was discovered via the study of transplanted tissue compatibility. Later studies revealed that tissue rejection due to incompatibility is only a facet of the full function of MHC molecules: binding an antigen derived from self-proteins, or from pathogens, and bringing the antigen presentation to the cell surface for recognition by the appropriate T-cells. MHC molecules mediate the interactions of leukocytes, also called white blood cells (WBCs), with other leukocytes or with body cells. The MHC determines donor compatibility for organ transplant, as well as one's susceptibility to autoimmune diseases. In a cell, protein molecules of the host's own phenotype or of other biologic entities ...
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Human Leukocyte Antigen
The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals. Mutations in HLA genes may be linked to autoimmune disease such as type I diabetes, and celiac disease. The HLA gene complex resides on a 3 Mbp stretch within chromosome 6, p-arm at 21.3. HLA genes are highly polymorphic, which means that they have many different alleles, allowing them to fine-tune the adaptive immune system. The proteins encoded by certain genes are also known as ''antigens'', as a result of their historic discovery as factors in organ transplants. HLAs corresponding to MHC class I ( A, B, and C), all of which are the HLA Class1 group, present peptides from inside the cell. For example, if the cell is infected by a virus, the HLA system brings fragme ...
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MHC Class I
MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called ''cytosolic'' or ''endogenous pathway''. In humans, the HLAs corresponding to MHC class I are HLA-A, HLA-B, and HLA-C. Function Class I MHC molecules bind peptides generated mainly from degradation of cytosolic proteins by the proteasome. The MHC I:peptide complex is then inserted via endoplasmic reticulum into the ext ...
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Beta-2 Microglobulin
β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells (excluding red blood cells). In humans, the β2 microglobulin protein is encoded by the ''B2M'' gene. Structure and function β2 microglobulin lies beside the α3 chain on the cell surface. Unlike α3, β2 has no transmembrane region. Directly above β2 (that is, further away from the cell) lies the α1 chain, which itself is next to the α2. β2 microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as CD1 (5 genes in humans), MR1, the neonatal Fc receptor (FcRn), and Qa-1 (a form of alloantigen). Nevertheless, the β2 microglobulin gene is outside of the MHC (HLA) locus, on a different chromosome. An additional function is association with the HFE protein, together regulating the expression of hepcidin in the liver which targets the iron transporte ...
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HLA-B
HLA-B (major histocompatibility complex, class I, B) is a human gene that provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria. HLA is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. Genes in this complex are separated into three basic groups: class I, class II, and class III. In humans, the HLA-B gene and two related genes, HLA-A and HLA-C, are the major genes in MHC class I. MHC class I genes provide instructions for making proteins that are present on the surface of almost all cells. On the cell surface, these proteins are bound to protein fragments (peptides) that have been exported from within the cell. MHC class I proteins display these peptides to t ...
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Chromosome 6
Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans more than 170 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total DNA in cells. It contains the major histocompatibility complex, which contains over 100 genes related to the immune response, and plays a vital role in organ transplantation. Genes The human leukocyte antigen lies on chromosome 6, with the exception of the gene for β2-microglobulin (which is located on chromosome 15), and encodes cell-surface antigen-presenting proteins among other functions. Number of genes In 2003, the entirety of chromosome 6 was manually annotated for proteins, resulting in the identification of 1,557 genes, and 633 pseudogenes. The following are some of the newer gene count estimates. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome var ...
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Calnexin
Calnexin (CNX) is 67kDaintegral protein (that appears variously as a 90kDa, 80kDa, or 75kDa band on western blotting depending on the source of the antibody) of the endoplasmic reticulum (ER). It consists of a large (50 kDa) N-terminal calcium- binding lumenal domain, a single transmembrane helix and a short (90 residues), acidic cytoplasmic tail. Function Calnexin is a chaperone, characterized by assisting protein folding and quality control, ensuring that only properly folded and assembled proteins proceed further along the secretory pathway. It specifically acts to retain unfolded or unassembled N-linked glycoproteins in the ER. Calnexin binds only those N-glycoproteins that have GlcNAc2Man9Glc1 oligosaccharides. These monoglucosylated oligosaccharides result from the trimming of two glucose residues by the sequential action of two glucosidases, I and II. Glucosidase II can also remove the third and last glucose residue. If the glycoprotein is not properly folded, an enz ...
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Chaperone Protein
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis. The first molecular chaperones discovered were a type of assembly chaperones which assist in the assembly of nucleosomes from folded histones and DNA. One major function of molecular chaperones is to prevent the aggregation of misfolded proteins, thus many chaperone proteins are classified as heat shock proteins, as the tendency for protein aggregation is increased by heat stress. The majority of molecular chaperones do not convey any steric information for protein folding, and instead assist in protein folding by binding to and stabilizing folding intermediat ...
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Peptide Loading Complex
The peptide-loading complex (PLC) is a short-lived, multisubunit membrane protein complex that is located in the endoplasmic reticulum (ER). It orchestrates peptide translocation and selection by MHC class I, major histocompatibility complex class I (MHC-I) molecules. Stable peptide-MHC I complexes are released to the cell surface to promote T-cell response against malignant or infected cells. In turn, T-cells recognize the activated peptides, which could be Immunogenicity , immunogenic or non-immunogenic. Overview A PLC assembly consists of seven subunits, including the transporters associated with antigen processing (TAP1 and TAP2 – jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the Chaperone (protein), chaperones tapasin and calreticulin. TAP transports proteasomal degradation products from the cytosol into the Lumen (anatomy) , lumen of the ER, where they are loaded onto MHC-I molecules. The peptide-MHC-I complexes then move via a secr ...
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HIV/AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual may not notice any symptoms, or may experience a brief period of influenza-like illness. Typically, this is followed by a prolonged incubation period with no symptoms. If the infection progresses, it interferes more with the immune system, increasing the risk of developing common infections such as tuberculosis, as well as other opportunistic infections, and tumors which are rare in people who have normal immune function. These late symptoms of infection are referred to as acquired immunodeficiency syndrome (AIDS). This stage is often also associated with unintended weight loss. HIV is spread primarily by unprotected sex (including anal and vaginal sex), contaminated blood transfusions, hypodermic needles, and from mother to ch ...
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