HLA-DPA1
Description
The HLA-DPA1 (major histocompatibility complex, class II, DP alpha 1) is a protein-coding gene located on chromosome 6.
Major histocompatibility complex, class II, DP alpha 1, also known as HLA-DPA1, is a human gene. The protein encoded by this gene belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DPA) and a beta chain (DPB), 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 one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane and the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules.
HLA-DPA1, also known as DP(W3), DP(W4), HLA-SB alpha chain, MHC class II DP3-alpha, is a component of the MHC class II molecule, a heterodimer that presents peptides to CD4+ T cells. It binds peptides derived from antigens that enter antigen-presenting cells (APCs) via endocytosis, displaying them on the cell surface for immune recognition. The peptide-binding cleft of HLA-DPA1 accommodates peptides of 10-30 residues. MHC class II presentation primarily relies on the degradation of proteins within the endocytic pathway by lysosomal proteases. This exogenous antigen presentation process involves the internalization of antigens by APCs, followed by their processing and presentation via MHC II molecules. While exogenous antigens are the primary targets, endogenous components derived from membrane proteins undergoing degradation in lysosomes can also compete for presentation. Autophagy, a cellular process that delivers cytoplasmic contents to lysosomes, contributes to the pool of endogenous peptides presented by MHC II molecules. Beyond APCs, certain epithelial cells in the gastrointestinal tract also express MHC class II molecules and CD74, acting as APCs. MHC class II molecule assembly involves the association of three MHC class II heterodimers (alpha and beta chains) with a CD74 trimer in the endoplasmic reticulum (ER), forming a heterononamer. Upon entering the endosomal/lysosomal system, CD74 is sequentially degraded by proteases, leaving a small fragment called CLIP (class-II-associated invariant chain peptide) bound to each MHC II molecule. HLA-DM facilitates CLIP removal by binding to the alpha-beta-CLIP complex, releasing CLIP and allowing high-affinity antigenic peptides to bind. HLA-DM stabilizes MHC II molecules until a suitable peptide is bound. The peptide-loaded MHC II molecule is then transported to the cell surface for presentation to T cells. In B cells, the interaction between HLA-DM and MHC II is regulated by HLA-DO. Primary dendritic cells (DCs) also express HLA-DO. The acidic environment of lysosomes plays a critical role in regulating antigen loading into MHC II molecules, promoting proteolysis and efficient peptide binding.
HLA-DPA1 is also known as DP(W3), DP(W4), DPA1, HLA-DP1A, HLA-DPA, HLA-DPB1, HLADP, HLASB, PLT1.
