A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DRB3-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells. Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (     , ). In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins (By similarity). Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance (By similarity). The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides. The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules (By similarity).
ALLELE DRB3*01:01: Exclusively presents several immunogenic epitopes derived from C. tetani neurotoxin tetX, playing a significant role in immune recognition and long-term protection ( ). Presents viral epitopes derived from HHV-6B U11, TRX2/U56 and U85 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection .
ALLELE DRB3*02:02 Exclusively presents several immunogenic epitopes derived from C. tetani neurotoxin tetX, playing a significant role in immune recognition and long-term protection (, ). Upon EBV infection, presents to CD4-positive T cells latent antigen EBNA2 (PRSPTVFYNIPPMPLPPSQL) and lytic antigen BZLF1 (LTAYHVSTAPTGSWF) peptides, driving oligoclonal expansion and selection of virus-specific memory T cell subsets with cytotoxic potential to directly eliminate virus-infected B cells (, ). Presents viral epitopes derived from HHV-6B U11, gB/U39 and gH/U48 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection . Plays a minor role in CD4-positive T cell immune response against Dengue virus by presenting conserved peptides from capsid and non-structural NS3 proteins . Displays peptides derived from IAV matrix protein M, implying a role in protection against IAV infection . In the context of tumor immunesurveillance, may present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies . Presents to Vbeta2-positive T-helper 1 cells specifically an immunodominant peptide derived from tumor antigen CTAG1A/NY-ESO-1(PGVLLKEFTVSGNILTIRLTAADHR) and confers protective memory response (, ). In metastatic epithelial tumors, presents to intratumoral CD4-positive T cells a TP53 neoantigen (HYNYMCNSSCMGSMNRRPILTIITL) carrying G245S hotspot driver mutation and may mediate tumor regression .
ALLELE DRB3*03:01: Presents a series of conserved peptides derived from the M. tuberculosis PPE family of proteins, in particular PPE29 and PPE33, known to be highly immunogenic . Presents immunogenic epitopes derived from C. tetani neurotoxin tetX, playing a role in immune recognition and long-term protection . Displays immunodominant viral peptides from HCV non-structural protein NS2, as part of a broad range T-helper response to resolve infection .
Subcellular locations: Cell membrane, Endoplasmic reticulum membrane, Lysosome membrane, Late endosome membrane, Autolysosome 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 . Component of immunological synapses at the interface between T cell and APC.
Expressed in professional APCs: monocyte/macrophages, dendritic cells and B cells (at protein level).