HLA-DRB5
Description
The HLA-DRB5 (major histocompatibility complex, class II, DR beta 5) is a protein-coding gene located on chromosome 6.
HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene. The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), 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 beta chain is approximately 26-28 kDa. It is encoded by 6 exons, exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. DRB1 is expressed at a level five times higher than its paralogues DRB3, DRB4 and DRB5.
HLA-DRB5, also known as DR beta-5, DR2-beta-2, Dw2, and MHC class II antigen DRB5, is a protein involved in the immune system's recognition of foreign antigens. It acts as a bridge between antigen-presenting cells (APCs) and CD4 T-cells, facilitating the immune response. HLA-DRB5 binds peptides derived from antigens that enter APCs through the endocytic pathway. These peptides, typically 10-30 amino acids long, are generated through degradation of proteins within lysosomes. The process of presenting these exogenous antigens via MHC II molecules is known as the exogenous pathway. This pathway is vital for immune system recognition of pathogens that have entered the body. Interestingly, HLA-DRB5 can also present peptides from self-proteins, suggesting its role in immune tolerance. Furthermore, HLA-DRB5, alongside other MHC class II molecules, forms a complex with the invariant chain (CD74) in the endoplasmic reticulum (ER). Upon entering the endosomal/lysosomal system, CD74 undergoes proteolytic degradation, leaving behind a fragment called CLIP. HLA-DM interacts with HLA-DRB5, removing CLIP and allowing for the binding of high-affinity antigenic peptides. The HLA-DRB5-peptide complex is then transported to the cell surface, presenting the antigen to CD4 T-cells. In B-cells, HLA-DO regulates the interaction between HLA-DM and MHC class II molecules, including HLA-DRB5. The lysosomal microenvironment plays a crucial role in antigen loading, with increased acidification promoting efficient peptide loading and processing.
HLA-DRB5 is also known as DRB5, HLA-DRB5*.
