HLA-DRB1 Antibody - #DF8360

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-DRB1-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. 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.

Allele DRB1*01:01: Displays an immunodominant epitope derived from Bacillus anthracis pagA/protective antigen, PA (KLPLYISNPNYKVNVYAVT), to both naive and PA-specific memory CD4-positive T cells. Presents immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (PHQFINLRSNNSATLIVPYV), contributing to viral clearance. Displays IAV and H5N1 HA-derived peptides (PKYVKQNTLKLAT and SNGNFIAPEYAYKIVK). Presents a self-peptide derived from COL4A3 (GWISLWKGFSF) to TCR (TRAV14 biased) on CD4-positive, FOXP3-positive regulatory T cells and mediates immune tolerance to self. Displays with low affinity a self-peptide derived from MBP (VHFFKNIVTPRTP).

Allele DRB1*03:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance. Displays self-peptides derived from retinal SAG (NRERRGIALDGKIKHE) and thyroid TG (LSSVVVDPSIRHFDV).

Allele DRB1*04:01: Presents an immunodominant bacterial epitope derived from M. tuberculosis esxB/culture filtrate antigen CFP-10 (EISTNIRQAGVQYSR), eliciting CD4-positive T cell effector functions such as IFNG production and cytotoxic activity. May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance. Presents tumor epitopes derived from melanoma-associated TYR antigen (QNILLSNAPLGPQFP and DYSYLQDSDPDSFQD), triggering CD4-positive T cell effector functions such as GMCSF production. Displays preferentially citrullinated self-peptides derived from VIM (GVYATR/citSSAVR and SAVRAR/citSSVPGVR) and ACAN (VVLLVATEGR/ CitVRVNSAYQDK). Displays self-peptides derived from COL2A1.

Allele DRB1*04:02: Displays native or citrullinated self-peptides derived from VIM.

Allele DRB1*04:04: May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (HIVMQYMYVPPGAPIPTTRN) and VP2 (RGDSTITSQDVANAVVGYGV), contributing to viral clearance. Displays preferentially citrullinated self-peptides derived from VIM (SAVRAR/citSSVPGVR).

Allele DRB1*05:01: Presents an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load.

Allele DRB1*07:01: May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (VPYVNAVPMDSMVRHNNWSL), contributing to viral clearance.

Allele DRB1*11:01: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load. May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SDRIIQITRGDSTITSQDVA), contributing to viral clearance. In the context of tumor immunesurveillance, may present tumor-derived neoantigens to CD4-positive T cells and trigger anti-tumor helper functions.

Allele DRB1*15:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SNNSATLIVPYVNAVPMDSM), contributing to viral clearance. Displays a self-peptide derived from MBP (ENPVVHFFKNIVTPR).

Allele DRB1*15:02: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load.

(Microbial infection) Acts as a receptor for Epstein-Barr virus on lymphocytes.

Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHCII.

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. Late endosome 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. Component of immunological synapses at the interface between T cell and APC.

Expressed in professional APCs: macrophages, dendritic cells and B cells.

Heterotrimer that consists of an alpha chain HLA-DRA1, a beta chain HLA-DRB1 and a peptide (peptide-MHCII). Newly synthesized alpha and beta chains forms a heterodimer (MHCII) that associates with the CD74/invariant chain (Ii) in the endoplasmic reticulum (ER). Ii is a trimer composed of three subunits and each subunit interacts with one MHCII dimer, blocking the peptide-binding cleft. As a result, MHCII molecules can not bind peptides present in the ER. The complex of MHCII and CD74/Ii is transported in vesicles from ER to Golgi to lysosomes, where it encounters antigenic peptides generated via proteolysis of endocytosed antigens. MHCII dimers are dissociated from CD74/Ii by the combined action of proteolysis and HLA-DM. Lysosomal enzymes such as cathepsin, degrade CD74/Ii leaving a 24 amino acid remnant called class II-associated Ii or CLIP. Interacts (via the peptide binding cleft) with CLIP; this interaction inhibits antigen peptide binding before entry in the endosomal compartment. The displacement of CLIP and replacement by a high affinity peptide in lysosomes is performed by HLA-DM heterodimer. HLA-DM catalyzes CLIP dissociation from MHCII, stabilizes empty MHCII and mediates the selection of high affinity peptides. Interacts with HLA-DM heterodimer; this interaction is direct. Interacts with TCR (via CDR3). Interacts (via beta-2 domain) with CD4 coreceptor (via Ig-like C2-type 1 domain); this interaction is of exceptionally low affinity yet necessary for optimal recognition of antigenic peptides.

(Microbial infection) Interacts with Staphylococcus aureus enterotoxin A/entA, enterotoxin B/entB, enterotoxin C1/entC1, entertoxin D/entD and enterotoxin H/entH. Enterotoxins bind outside the peptide-binding cleft of MHCII: enterotoxin H/entH interacts via the beta-1 domain of MHCII and in a zinc-dependent way, whereas enterotoxin B/entB interacts primarily via the alpha-1 domain.

(Microbial infection) Interacts with Epstein-Barr virus gp42 protein.

The beta-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the alpha-1 domain of HLA-DRA. Forms hydrogen bonds with the peptide main chain via conserved amino acid in most HLA-DRB molecules. The polymorphic residues accomodate the side chains of the peptide conferring peptide specificity to distinct HLA-DRB1 alleles (PubMed:8145819, PubMed:28467828, PubMed:9782128, PubMed:9354468). The peptide-bound beta-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domains of the T cell receptor (PubMed:19303388).

The beta-2 Ig-like domain mediates the interaction with CD4 coreceptor.