HLA class II histocompatibility antigen, DRB1 beta chain is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''HLA-DRB1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. DRB1 encodes the most prevalent beta subunit of

HLA-DR HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR (Human Leukocyte Antigen – DR isotype) and peptide, generally between 9 and 30 amino acids in ...

. DRB1 alleles, especially those encoding amino acid sequence changes at positions 11 and 13, are associated risk of

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

Function

The

encoded by this gene belongs to the HLA class II beta chain

paralogues Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...

. 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 The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

by presenting peptides derived from extracellular proteins to

T helper cell The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

s. Class II molecules are constitutively expressed in professional

antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...

s (APC: B lymphocytes, dendritic cells, macrophages), and could be induced in non-professional APCs. There is evidence it is associated with reduced severity of COVID-19 disease.

Gene structure and polymorphisms

The beta chain is approximately 26-28 kDa. It is encoded by 6

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s, exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...

domain and exon 5 encodes the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

ic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

s have been described and typing for these polymorphisms is routinely done for bone marrow and kidney transplantation.

Gene expression

DRB1 is expressed at a level five times higher than its paralogues DRB3, DRB4 and DRB5. DRB1 is present in all individuals. Allelic variants of DRB1 are linked with either none or one of the genes DRB3, DRB4 and DRB5. There are 5 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. Prevalence of the HLA-DRB1*10:01 allele was greatly increased in people with

anti-IgLON5 disease Anti-IgLON5 disease is a neurodegenerative autoimmune disease. It is marked by parasomnias and chorea - an involuntary movement disorder. __TOC__ Pathophysiology The IgLON proteins are a family of five cell-adhesion molecules IgLON 1, 2, 3, 4 ...

Function

Gene structure and polymorphisms

Gene expression

See also

References

Further reading