Summary
Application
FC, IF, IHC, WB
Basic Information
Immunogen
Activated human peripheral blood mononuclear cells
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.
Target
Alternative Names
DRB1, HLA class II histocompatibility antigen, DR-1 beta chain, HLA-DR-beta 1, HLA-DRB1, human leucocyte antigen DRB1, Leucocyte antigen DR beta 1 chain, lymphocyte antigen DRB1, major histocompatibility complex, class II, DR beta 1, MHC class II HLA-DR beta 1 chain, MHC class II HLA-DR-beta cell surface glycoprotein
Biological Process
Antigen processing and presentation of endogenous peptide antigen via MHC class II Source: UniProtKB
Antigen processing and presentation of exogenous peptide antigen via MHC class II Source: UniProtKB
Detection of bacterium Source: UniProtKB
Epidermis development Source: UniProtKB
Humoral immune response Source: UniProtKB
Immune response Source: UniProtKB
Inflammatory response to antigenic stimulus Source: UniProtKB
Macrophage differentiation Source: ARUK-UCL
Myeloid dendritic cell antigen processing and presentation Source: UniProtKB
Negative regulation of inflammatory response to antigenic stimulus Source: UniProtKB
Negative regulation of interferon-gamma production Source: UniProtKB
Negative regulation of T cell proliferation Source: UniProtKB
Peptide antigen assembly with MHC class II protein complex Source: UniProtKB
Positive regulation of CD4-positive, alpha-beta T cell activation Source: UniProtKB
Positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: CAFA
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: CAFA
Positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
Positive regulation of kinase activity Source: CAFA
Positive regulation of MAPK cascade Source: CAFA
Positive regulation of memory T cell differentiation Source: UniProtKB
Positive regulation of monocyte differentiation Source: CAFA
Positive regulation of protein phosphorylation Source: CAFA
Positive regulation of T cell activation Source: GO_Central
Positive regulation of T cell mediated cytotoxicity Source: UniProtKB
Positive regulation of T cell mediated immune response to tumor cell Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: CAFA
Positive regulation of viral entry into host cell Source: CAFA
Protein tetramerization Source: UniProtKB
Regulation of interleukin-10 production Source: UniProtKB
Regulation of interleukin-4 production Source: UniProtKB
Regulation of T-helper cell differentiation Source: UniProtKB
Signal transduction Source: UniProtKB
T cell receptor signaling pathway Source: UniProtKB
T-helper 1 type immune response Source: UniProtKB
Cellular Location
Late endosome membrane; Lysosome membrane; Autolysosome membrane; Endoplasmic reticulum membrane; Cell membrane. 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 (PubMed:18305173). Component of immunological synapses at the interface between T cell and APC (PubMed:29884618).
Involvement in disease
In populations of European descent, allele DRB1*01:03 is associated with increased susceptibility to Crohn disease and colonic ulcerative colitis. Decreased heterozygosity in individuals with colonic ulcerative colitis suggests that it acts as a recessive risk allele.
Sarcoidosis 1 (SS1):
Disease susceptibility is associated with variants affecting the gene represented in this entry. Alleles DRB1*04:02, DRB1*11:01 and DRB1*12:01 are associated with sarcoidosis. Allele DRB1*04:02 is significantly associated with specific sarcodosis phenotypes such as eye, parotid and salivary gland involvement. An idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.
Multiple sclerosis (MS):
Disease susceptibility is associated with variants affecting the gene represented in this entry. In populations of European descent, allele DRB1*15:01 has the strongest association with multiple sclerosis among all HLA class II alleles. Additional risk is associated with the strongly linked alleles DRB1*03:01 and DQB1*02:01 as well as with allele DRB1*13:03 (PubMed:21833088). It is postulated that bacterial or viral infection triggers the autoimmune MS. Microbial peptides having low affinity crossreactivity to MBP autoantigen, may stimulate autoreactive T cells via molecular mimicry and initiate the autoimmune inflammation (PubMed:19303388). A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease.
Allele DRB1*15:01 is associated with increased susceptibility to Goodpasture syndrome. Can present a self-peptide derived from COL4A3 (GWISLWKGFSF) on TCR (TRAV19 biased) in pathogenic CD4-positive T-helper 1 and T-helper 17 cells, triggering autoimmune inflammation.
Rheumatoid arthritis (RA):
Disease susceptibility is associated with variants affecting the gene represented in this entry. Alleles DRB1*04:01; DRB1*04:04; DRB1*04:05; DRB1*04:08; DRB1*10:01; DRB1*01:01 and DRB1*01:02 are associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis). Variations at position 40 in the peptide-binding cleft of these alleles explain most of the association to rheumatoid arthritis risk. An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
Topology
Extracellular: 30-227
Helical: 228-248
Cytoplasmic: 249-266
PTM
Ubiquitinated by MARCHF1 and MARCHF8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHCII.