Recombinant Human HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1), Truncated

Uniprot Id

P01909

Target Species

Human

Target Name

HLA-DQA1

Target Full Name

HLA class II histocompatibility antigen, DQ alpha 1 chain

Target Function

Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.

Target Subcellular Location

Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Note=The MHC class II complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation.

Target Protein Families

MHC class II family

Target Research Area

Immunology

Target Synonyms

CD; CELIAC1; DC 1 alpha chain; DC alpha; DC-1 alpha chain; DC-alpha; DC1; included; DQ alpha 1 chain; DQ-A1; DQ-DRW9 alpha chain; DQA1_HUMAN; FLJ27088; FLJ27328; Gluten-sensitive enteropathy (celiac disease); GSE; HLA class II histocompatibility antigen; HLA class II histocompatibility antigen; DQ alpha 1 chain; HLA class II histocompatibility antigen; DQ(W3) alpha chain; HLA-DCA; HLA-DQA; HLA-DQA1; HLA-DQA1 major histocompatibility complex; class II; DQ alpha 1; HLADC histocompatibility type; Immune response antigens HIa; included; leucocyte antigen DQA1 ; leukocyte antigen alpha chain ; LOC100133678; LOC100507686; LOC100509457; Major histocompatibility complex; class II; DQ alpha 1; MGC149527; MHC class II antigen; MHC class II DQA1; MHC class II HLA-D alpha glycoprotein; MHC class II HLA-DQ alpha 1; MHC class II surface glycoprotein; MHC HLA-DQ alpha; OTTHUMP00000029141; OTTHUMP00000176885; OTTHUMP00000178551; OTTHUMP00000178552; OTTHUMP00000233817

Target Background

HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation.