Search results for B2M

Showing 17 results out of 23

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Protein (5 results from a total of 11)

Identifier: R-HSA-167743
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: B2M: P61769
Identifier: R-HSA-182298
Species: Homo sapiens
Compartment: early endosome membrane
Primary external reference: UniProt: B2M: P61769
Identifier: R-HSA-6806144
Species: Homo sapiens
Compartment: specific granule lumen
Primary external reference: UniProt: B2M: P61769
Identifier: R-HSA-1236891
Species: Homo sapiens
Compartment: phagocytic vesicle membrane
Primary external reference: UniProt: B2M: P61769
Identifier: R-HSA-983403
Species: Homo sapiens
Compartment: Golgi membrane
Primary external reference: UniProt: P61769

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8962826
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000166710

Reaction (5 results from a total of 5)

Identifier: R-HSA-9637635
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
Mtb 6 kDa early secretory antigenic target (esxA) binds to freely available human beta-2-microglobulin (B2M) in the endoplasmic reticulum lumen, inhibiting the loading of antigen-derived peptides to B2M, a component of the class I major histocompatibility complex (MHC-I complex) (Sreejit et al. 2014).
Identifier: R-HSA-983146
Species: Homo sapiens
Compartment: integral component of lumenal side of endoplasmic reticulum membrane, endoplasmic reticulum lumen
Interaction of calnexin (CNX) with MHC class I HC stabilizes it and facilitates the association of the beta2 microglobulin component (B2M). The two chains are linked noncovalently via interaction of B2M and the alpha3 domain of MHC HC. After formation of the HC:B2M heterodimer, the MHC complex dissociates from CNX.
Identifier: R-HSA-983142
Species: Homo sapiens
Compartment: integral component of lumenal side of endoplasmic reticulum membrane, endoplasmic reticulum membrane, endoplasmic reticulum lumen
Upon interaction of Beta-2-microglobin (B2M) with MHC class I Heavy Chain (HC), calnexin is fully replaced by its soluble ortholog calreticulin (CRT) and this complex is incorporated into the peptide loading complex (PLC). PLC is a multiprotein complex that includes CRT, ERp57 and the additional components tapasin, transporter associated with antigen processing (TAP) and Bap31. The stoichometry of components in PLC remains unclear. The PLC loads antigenic peptides onto MHC class I molecules; components of the PLC cooperate to stabilize the MHC class I complex and optimally load peptides. Tapasin is a type I transmembrane protein that interacts directly with TAP and tethers the MHC complex to it. TAP facilitates the transport of peptides from the cytosol to the ER lumen. B cell receptor–associated protein (Bap31), a putative cargo receptor, associates with HC and acts as a retrograde transporter, carrying peptide-loaded class I MHC molecules.
Identifier: R-HSA-8850326
Species: Homo sapiens
Compartment: plasma membrane
T lymphocytes have developed the capacity to recognize as antigens a large variety of molecules including peptides, lipids, and vitamin metabolites (Moody DB et al. 2005; Rossjohn J et al. 2015; de Jong A 2015). Specific recognition of lipids by T-cell receptors (TCR) occurs when these molecules form antigenic complexes using functionally nonpolymorphic CD1 molecules (Beckman EM et al. 1994; De Libero G1 & Mori L 2005; Tatituri RV et al. 2013; Van Rhijn I et al. 2015).

Humans express five functional CD1 isotypes (CD1a-e), with CD1e being the only member that does not directly present antigens to T cells (Calabi F et al. 1989; Balk SP et al. 1989; de la Salle H et al. 2005). CD1a, CD1b, CD1c and CD1d are surface expressed proteins that can be found on the plasma membranes of antigen-presenting cells (APC) (Dougan SK et al. 2007). CD1 ectodomains consist of a heavy chain, which folds into three extracellular domains (alpha1, alpha2 and alpha3) noncovalently associated with beta2-microglobulin (B2M) (Moody DB et al. 2005). Antigen-binding grooves nestle between the alpha1 and alpha2 helices and are mostly lined by hydrophobic residues (Zeng Z et al. 1997). This allows the antigenic lipids to be anchored via their hydrophobic chains, so that polar motifs protrude toward the aqueous milieu (Gadola SD et al. 2002; Zajonc DM et al. 2003, 2005; Batuwangala T et al. 2004; Koch M et al. 2005; Zajonc DM et al. 2005; Scharf L et al. 2010; Garcia-Alles LF et al. 2011). Consequently, polar heads establish stimulatory contacts with TCRs, while variation in the number, length and saturation of alkyl chains may contribute to the binding to varying degrees (Borg NA et al. 2007; Garcia-Alles LF et al. 2011; Li Y et al. 2010; Pierce BG et al. 2014). Each of the four CD1 isoforms that directly present antigens to T cells differ in size of the antigen-binding grooves (Zajonc DM et al. 2005; Gadola SD et al. 2002; Zajonc DM et al. 2003, 2005; Batuwangala T et al. 2004; Koch M et al. 2005; Cheng TY et al. 2006; Borg NA et al. 2007; Scharf L et al. 2010; Garcia-Alles LF et al. 2011), intracellular trafficking patterns (Sugita M et al. 1999; Moody DB & Porcelli SA 2003), lipid ligand repertoire (Im JS et al. 2004; Huang S et al. 2011; Ly D & Moody DB 2014), and tissue distribution of expression (Dougan SK et al. 2007). Together with the observation that multiple CD1 isoforms have been maintained throughout mammalian evolution, this argues that each CD1 isoform plays a non-redundant role in the immune system (Dascher CC 2007; de Jong A 2015).

A large spectrum of self- and foreign lipids associates with members of CD1 family (Mattner J et al. 2005; Kinjo Y et al. 2005; Chang DH et al. 2008; Cohen NR et al. 2009; De Libero G et al. 2009; Zajonc DM & Girardi E 2015; Birkinshaw RW et al. 2015; de Jong A 2015). CD1-bound self-derived lipid antigens, including gangliosides, sulfatide, phosphoglycerolipids and sphingomyelin, can stimulate specialized subsets of T cells though the importance of self-lipid interactions with TCRs can vary (Birkinshaw RW et al. 2015; Borg NA et al. 2007; Luoma AM et al. 2013, 2014; Lepore M et al. 2014; Roy S et al. 2016). The ability of of both alphabeta and gammadelta T cells to recognize self lipid loaded CD1 molecules enables these lymphocytes to sense changes in the lipid composition of cells and tissues as a result of infections, inflammation, or malignancies (Brennan PJ et al. 2011; Chang DH et al. 2008; Cohen NR et al. 2009; Luoma et al. 2014; Lepore M et al. 2014; de Jong A 2014, 2015).

The Reactome event shows self lipid-based molecules that have been reported to function as antigens for CD1-restricted T cells (Shamshiev A et al. 2002; Birkinshaw RW et al. 2015; de Jong A 2015).

Identifier: R-HSA-8850356
Species: Homo sapiens
Compartment: plasma membrane
The hallmark of T cell activation is the direct binding of T-cell receptor (TCR) to an antigen that is presented by an antigen-presenting molecule. TCRs are able to recognize as antigens a large variety of molecules including peptides, lipids, and vitamin metabolites (Moody DB et al. 2005; Rossjohn J et al. 2015; de Jong A 2015). While TCR responds to peptides when they are presented by classical major histocompatibility complex (MHC)-encoded class I or II molecules, specific recognition of lipids by TCR occurs when lipid-based antigens form antigenic complexes with CD1 antigen-presenting molecules (Garboczi DN et al. 1996; Beckman EM et al. 1994; De Libero G1 & Mori L 2005; Tatituri RV et al. 2013; Van Rhijn I et al. 2015).

Humans express five functional CD1 isotypes (CD1a-e), with CD1e being the only member that does not directly present antigens to T cells (Calabi F et al. 1989; Balk SP et al. 1989; de la Salle H et al. 2005). CD1a, CD1b, CD1c and CD1d are surface expressed proteins that can be found on the plasma membranes of antigen-presenting cells (APC) (Dougan SK et al. 2007). CD1 ectodomains consist of a heavy chain, which folds into three extracellular domains (alpha1, alpha2 and alpha3) noncovalently associated with beta2-microglobulin (B2M) (Moody DB et al. 2005). Antigen-binding grooves nestle between the alpha1 and alpha2 helices and are mostly lined by hydrophobic residues (Zeng Z et al. 1997). This allows the antigenic lipids to be anchored via their hydrophobic chains, so that polar motifs protrude toward the aqueous milieu (Gadola SD et al. 2002; Zajonc DM et al. 2003, 2005; Batuwangala T et al. 2004; Koch M et al. 2005; Zajonc DM et al. 2005; Scharf L et al. 2010; Garcia-Alles LF et al. 2011). Consequently, polar heads establish stimulatory contacts with TCRs, while variation in the number, length and saturation of alkyl chains may contribute to the binding to varying degrees (Borg NA et al. 2007; Garcia-Alles LF et al. 2011; Li Y et al. 2010; Pei B et al 2012; Pierce BG et al. 2014). Each of the four CD1 isoforms that directly present antigens to T cells differ in size of the antigen-binding grooves (Zajonc DM et al. 2005; Gadola SD et al. 2002; Zajonc DM et al. 2003, 2005; Batuwangala T et al. 2004; Koch M et al. 2005; Cheng TY et al. 2006; Borg NA et al. 2007; Scharf L et al. 2010; Garcia-Alles LF et al. 2011), intracellular trafficking patterns (Sugita M et al. 1999; Moody DB & Porcelli SA 2003), lipid ligand repertoire (Im JS et al. 2004; Huang S et al. 2011; Ly D & Moody DB 2014), and tissue distribution of expression (Dougan SK et al. 2007). Together with the observation that multiple CD1 isoforms have been maintained throughout mammalian evolution, this argues that each CD1 isoform plays a non-redundant role in the immune system (Dascher CC 2007; de Jong A 2015).

T cells recognize both endogenous and exogenous (derived from intracellular microbial pathogens) lipid antigens bound to CD1 molecules (Mattner J et al. 2005; Kinjo Y et al. 2005; Chang DH et al. 2008; Cohen NR et al. 2009; De Libero G et al. 2009; Zajonc DM & Girardi E 2015; Birkinshaw RW et al. 2015; de Jong A 2015). Foreign lipid antigens are extremely diverse chemically and include naturally occurring lipopeptide, glycolipids and phospholipid structures that are distinct from mammalian lipids (Moran A 2009). The best studied lipid antigens of microbial origin are glycolipids derived from the cell envelope of Mycobacteria species (De Libero G et al. 2009). They include CD1b-restricted foreign lipid antigens such as lipoarabinomannan (LAM), lipomannan (LM), phosphatidylinositol mannosides (PIM), mycolic acid, glucose monomycolate (GMM), glycerol monomycolate and diacylated sulpholipids (Sieling PA et al. 1995; Moody DB et al. 2000; Layre E et al. 2009; Gilleron M et al. 2004; Kasmar AG et al. 2011). While most mammalian glycolipids have beta-linked carbohydrates attached to the lipid backbone, bacterial glycolipids typically have alpha-linkage. The structural difference in the linkage may contribute to the highly specific interaction of the TCR with the CD1:lipid antigen complex thus dictating the outcome of the immune response (Scott-Browne JP et al. 2007; Zajonc DM et al. 2005, 2007). In addition, lipopeptides, such as didehydroxymycobactin (DDM), an intermediate in the biosynthesis of the mycobacterial iron scavenger mycobactin siderophores, can be recognized by CD1a-restricted T cells (Moody DB et al. 2004; Zajonc DM et al. 2005). Diacylglycerols, such as the alpha-galactosyldiacylglycerol from the spirochete Borrelia burgdorferi or an alpha-linkage glycosphingolipid (alpha-glucuronosylceramide) found in alpha-proteobacteria can be presented by CD1d to stimulate invariant natural killer T (iNKT) cells (Sriram V et al. 2005; Kinjo Y et al. 2006). The ability of T cells to see lipid antigens bound to CD1 proteins enables these lymphocytes to sense changes in the lipid composition of cells and tissues as a result of infections or inflammation (Mattner J et al. 2005; Kinjo Y et al. 2005; Chang DH et al. 2008; Cohen NR et al. 2009; de Jong A 2015).

The Reactome event shows foreign lipid-based molecules that have been reported to function as antigens for CD1-restricted T cells (Batuwangala T et al. 2004; Roy S et al. 2014; Garcia-Alles LF et al. 2011; Wang J et al. 2010; Sieling PA et al. 1995; Guiard J et al. 2009; Kasmar AG et al. 2011).

Set (2 results from a total of 2)

Identifier: R-HSA-8850280
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-8848835
Species: Homo sapiens
Compartment: plasma membrane

Complex (2 results from a total of 2)

Identifier: R-HSA-8850222
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-8848850
Species: Homo sapiens
Compartment: plasma membrane

Pathway (2 results from a total of 2)

Identifier: R-HSA-983170
Species: Homo sapiens
Unlike other glycoproteins, correct folding of MHC class I molecules is not sufficient to trigger their exit from the ER, they exit only after peptide loading. Described here is the process of antigen presentation which consists of the folding, assembly, and peptide loading of MHC class I molecules. The newly synthesized MHC class I Heavy Chain (HC) is initially folded with the help of several chaperones (calnexin, BiP, ERp57) and then binds with Beta-2-microglobulin (B2M). This MHC:B2M heterodimer enters the peptide loading complex (PLC), a multiprotein complex that includes calreticulin, endoplasmic reticulum resident protein 57 (ERp57), transporter associated with antigen processing (TAP) and tapasin. Peptides generated from Ub-proteolysis are transported into the ER through TAP. These peptides are further trimmed by ER-associated aminopeptidase (ERAP) and loaded on to MHC class I molecules. Stable MHC class I trimers with high-affinity peptide are transported from the ER to the cell surface by the Golgi apparatus.
Identifier: R-HSA-983169
Species: Homo sapiens
Major histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular bacteria or tumor-associated antigens. They bind peptide fragments of these proteins and presenting them to CD8+ T cells at the cell surface. This enables cytotoxic T cells to identify and eliminate cells that are synthesizing abnormal or foreign proteins. MHC class I is a trimeric complex composed of a polymorphic heavy chain (HC or alpha chain) and an invariable light chain, known as beta2-microglobulin (B2M) plus an 8-10 residue peptide ligand. Represented here are the events in the biosynthesis of MHC class I molecules, including generation of antigenic peptides by the ubiquitin/26S-proteasome system, delivery of these peptides to the endoplasmic reticulum (ER), loading of peptides to MHC class I molecules and display of MHC class I complexes on the cell surface.
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