HLA-DP is a protein/peptide-antigen

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

and

graft-versus-host disease Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which remain wit ...

antigen that is composed of 2 subunits, DPα and DPβ. DPα and DPβ are encoded by two loci,

HLA-DPA1 Major histocompatibility complex, class II, DP alpha 1, also known as HLA-DPA1, is a human gene. Function The protein encoded by this gene belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting o ...

and

HLA-DPB1 HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the ''HLA-DPB1'' gene. HLA-DPB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha ( ...

, that are found in the MHC Class II (or HLA-D) region in the

Human Leukocyte Antigen The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of th ...

complex on human chromosome 6 (see protein boxes on right for links). Less is known about HLA-DP relative to

HLA-DQ HLA-DQ (DQ) is a cell surface receptor protein found on antigen-presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromos ...

and

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 ...

but the sequencing of DP types and determination of more frequent

haplotype A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...

s has progressed greatly within the last few years.

Structure, Functions, Genetics

Structure

HLA-DP is an αβ-

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

cell-surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral me ...

. Each DP subunit (α-subunit, β-subunit) is composed of a α-helical N-terminal domain, an IgG-like β-sheet, a membrane spanning domain, and a cytoplasmic domain. The α-helical domain forms the sides of the peptide binding groove. The β-sheet regions form the base of the binding groove and the bulk of the molecule as well as the inter-subunit (non-covalent) binding region.

Function

The name 'HLA-DP' originally describes a transplantation antigen of

MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, ...

category of the

major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are calle ...

of humans, however this antigen is an artifact of the era of organ transplantation. HLA DP functions as a cell surface receptor for foreign or self antigens. The immune system surveys antigens for foreign pathogens when presented by MHC receptors (like HLA-DP). The MHC Class II antigens are found on

antigen presenting cells 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 ...

(APC)(macrophages, dendritic cells, and B-lymphocytes). Normally, these APC 'present' class II receptor/antigens to a great many T-cells, each with unique T-cell receptor (TCR) variants. A few TCR variants that recognize these DQ/antigen complexes are on CD4 positive T-cells. These T-cells, called T-helper (T_h) cells, can promote the amplification of B-cells that recognize a different portion of the same antigen. Alternatively, macrophages and other cytotoxic lymphocytes consume or destroy cells by apoptotic signaling and present self-antigens. Self antigens, in the right context, form a regulatory T-cell population that protects self tissues from immune attack or autoimmunity.

Genetics

The α-chain and β- of DP is encoded by the HLA-DPA1 locus and HLA-DPB1 loci, respectively. This cluster is located at the proximal (centromeric) end of the HLA superlocus in human chromosome 6p21.31. It is distal from

and

encoding loci and therefore is much more equilibrated with respect to other HLA loci. In the ''Super B8'' complex DP locus is more frequently substituted, either as a result of its distance from other loci, or because it was not as actively selected in the evolution of ''Super B8''.

Understanding the Heterodimeric DP Isoforms

Each combination of DPA1 allele gene product with each combination of DPB1 'gene' product can potentially recombine to produce one isoform. DP genes are highly variable in the human population. In a typical population there are many DP alpha and beta. Most isoforms are not common. These 'cis'-isoforms will account for at least 50% of the DP isoforms. The other, trans isoforms are typically more rare, isoforms result from random 'trans' combinations of haplotypes in individuals as a result of 'trans' paternal/maternal gene product isoforms.

Alleles

HLA-DPA1 Alleles HLA-DPB1 Alleles

HLA-DPB1 Allele Nomenclature Change

Before the April 2010 HLA nomenclature update, new HLA-DPB1 allele names were assigned within the existing nomenclature system. For example, the allele discovered after HLA-DPB1*9901 was assigned as DPB1*0102, the subsequent allele was named DPB1*0202, then *0302 and so on. This name assignment was decided because of the complex genetic characteristics of DPB1 alleles compared to alleles of other HLA loci. The majority of the HLA-DPB1 alleles cannot be simply grouped together by their nucleotide sequences. This name assignment has been the most confusing system within the HLA nomenclature. In the 2010 HLA nomenclature update, all DPB1 alleles, except DPB1*0202 and *0402, discovered after DPB1*9901 were reassigned with new numbers. For example, DPB1*0102 becomes DPB1*100:01 and DPB1*0203 becomes DPB1*101:01. All renamed alleles are listed in the HLA-DPB1 Nomenclature Conversion Chart below.ftp://ftp.ebi.ac.uk/pub/databases/imgt/mhc/hla/Nomenclature_2009.txt To aid in migration of data to the new nomenclature the WHO Nomenclature Committee for Factors of the HLA System has provided th
IMGT/HLA Nomenclature Conversion Tool
. This tool allows you to enter an HLA allele name and will provide you with both the current and new versions of the allele name. New alleles that have never been assigned with a name prior to the April 2010 update are: