HLA-DRB1 Gene and Protein Function
HLA-DRB1 is part of the HLA class II beta chain paralogs. The class II molecule is a heterodimer composed of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. This molecule is crucial in the immune system as it presents peptides from extracellular proteins. Class II molecules are expressed on antigen-presenting cells. The beta chain, approximately 26-28 kDa, is encoded by six exons. Exon one encodes the leader peptide; exons two and three encode the two extracellular domains; exon four encodes the transmembrane domain; and exon five encodes the cytoplasmic tail. The beta chain contains all polymorphisms that determine peptide binding specificities. Hundreds of DRB1 alleles exist, some of which are associated with certain diseases. For instance, DRB1*1302 is linked to the persistence of acute and chronic hepatitis B virus. Additionally, this gene has multiple pseudogenes.
Gene and Protein Complex Functionality
HLA-DRB1 facilitates several functions, including MHC class II receptor activity, peptide antigen binding, and signaling receptor binding. It is involved in processes such as the positive regulation of immune response, gene expression regulation, and leukocyte differentiation. This gene's products are located in the bounding membrane of organelles, on the external side of the plasma membrane, and within the immunological synapse. HLA-DRB1 is part of the MHC class II protein complex and is implicated in various diseases, including asthma, autoimmune diseases, bacterial infectious diseases, eye diseases, and sarcoidosis. It also serves as a biomarker for toxic shock syndrome.
Detailed Function and Structure
The HLA-DRB1 gene provides instructions for a protein essential to the immune system. It is part of the human leukocyte antigen (HLA) complex, which helps the immune system differentiate between the body’s proteins and those of foreign invaders, such as viruses and bacteria. The HLA complex is the human equivalent of the major histocompatibility complex (MHC) found in many species. HLA-DRB1 belongs to the MHC class II group, which encodes proteins present on the surface of certain immune cells. These proteins bind to extracellular peptides and display them to the immune system, prompting a response if they are identified as foreign.
The beta chain produced by HLA-DRB1 binds to the alpha chain produced by the HLA-DRA gene, forming the HLA-DR antigen-binding heterodimer. This complex displays foreign peptides to the immune system, triggering an immune response. Each MHC class II gene has numerous variations, enabling the immune system to respond to various foreign invaders. Researchers have identified hundreds of HLA-DRB1 alleles, each designated by a unique number (e.g., HLA-DRB1*04:01).
Allele DRB1*01:01
- Bacillus anthracis pagA/protective antigen, PA: KLPLYISNPNYKVNVYAVT
- HIV-1 gag peptide: FRDYVDRFYKTLRAEQASQE
- HRV-16 capsid proteins:
- VP1: PRFSLPFLSIASAYYMFYDG
- VP2: PHQFINLRSNNSATLIVPYV
- IAV external protein HA:
- PKYVKQNTLKLAT
- SNGNFIAPEYAYKIVK
- IAV internal proteins M, NP, and PB1:
- M-derived epitope: GLIYNRMGAVTTEV
- COL4A3: GWISLWKGFSF
- MBP: VHFFKNIVTPRTP
Allele DRB1*03:01
- HRV-16 capsid protein VP2: NEKQPSDDNWLNFDGTLLGN
- Retinal SAG: NRERRGIALDGKIKHE
- Thyroid TG: LSSVVVDPSIRHFDV
- HHV-6B gH/U48 and U85 antigens (no specific peptide sequences provided)
- C. tetani neurotoxin tetX (no specific peptide sequences provided)
Allele DRB1*04:01
- M. tuberculosis esxB/culture filtrate antigen CFP-10: EISTNIRQAGVQYSR
- HRV-16 capsid protein VP2: NEKQPSDDNWLNFDGTLLGN
- Melanoma-associated TYR antigen:
- QNILLSNAPLGPQFP
- DYSYLQDSDPDSFQD
- VIM:
- GVYATR/citSSAVR
- SAVRAR/citSSVPGVR
- ACAN: VVLLVATEGR/CitVRVNSAYQDK
- COL2A1 (no specific peptide sequences provided)
Allele DRB1*04:02
- VIM: Native or citrullinated self-peptides (no specific sequences provided)
Allele DRB1*04:04
- HRV-16 capsid proteins:
- VP1: HIVMQYMYVPPGAPIPTTRN
- VP2: RGDSTITSQDVANAVVGYGV
- VIM: SAVRAR/citSSVPGVR
Allele DRB1*04:05
- Tumor-associated antigen WT1: KRYFKLSHLQMHSRKH
Allele DRB1*05:01
- HIV-1 gag peptide: FRDYVDRFYKTLRAEQASQE
Allele DRB1*07:01
- EBV latent antigen EBNA2 peptide: PRSPTVFYNIPPMPLPPSQL
- HRV-16 capsid proteins:
- VP1: PRFSLPFLSIASAYYMFYDG
- VP2: VPYVNAVPMDSMVRHNNWSL
- Tumor-associated antigen WT1: MTEYKLVVVGAVGVGKSALTIQLI
- KRAS neoantigen: MTEYKLVVVGAVGVGKSALTIQLI (G12V mutation)
Allele DRB1*11:01
- HIV-1 gag peptide: FRDYVDRFYKTLRAEQASQE
- HRV-16 capsid protein VP2: SDRIIQITRGDSTITSQDVA
- C. tetani neurotoxin tetX (no specific peptide sequences provided)
Allele DRB1*13:01
- HHV-6B antigens (no specific peptide sequences provided)
Allele DRB1*15:01
- HRV-16 capsid protein VP2: SNNSATLIVPYVNAVPMDSM
- MBP: ENPVVHFFKNIVTPR
- Tumor-associated antigen WT1: KRYFKLSHLQMHSRKH
Allele DRB1*15:02
- HIV-1 gag peptide: FRDYVDRFYKTLRAEQASQE
- Tumor-associated antigen WT1: KRYFKLSHLQMHSRKH