HLA-DP

Last updated • 4 min readFrom Wikipedia, The Free Encyclopedia
MHC class II, DP
(heterodimer)
Protein type cell surface receptor
FunctionImmune recognition and
antigen presentation
Subunit nameGeneChromosomal locus
α HLA-DPA1 Chromosome 6p21.31
β HLA-DPB1 Chromosome 6p21.31

HLA-DP is a protein/peptide-antigen receptor and graft-versus-host disease antigen that is composed of 2 subunits, DPα and DPβ. DPα and DPβ are encoded by two loci, HLA-DPA1 and HLA-DPB1, that are found in the MHC Class II (or HLA-D) region in the Human Leukocyte Antigen complex on human chromosome 6 (see protein boxes on right for links). Less is known about HLA-DP relative to HLA-DQ and HLA-DR but the sequencing of DP types and determination of more frequent haplotypes has progressed greatly within the last few years.

Contents

Structure, Functions, Genetics

HLA DP Receptor with bound peptide and TCR DP Pept TCR.JPG
HLA DP Receptor with bound peptide and TCR

Structure

HLA-DP is an αβ-heterodimer cell-surface receptor. 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 category of the major histocompatibility complex 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 (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 (Th) 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 HLA-DR and HLA-DQ 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

DP(αβ) Isoforms given one maternal (m) and one paternal (p) chromosome 6
HLADPB1
allele(m)(p)
DPA1(m)αmβm (Cis m)αmβp (Trans)
(p)αpβm (Trans)αpβp (Cis p)
Result: 2 Cis, αmβm & αpβp, isoforms and 2 trans,αmβp & αpβm.

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-DPA1
*01*02*03*04
*01:03
*01:04
*01:05
*01:06
*01:07
*01:08
*01:09
*01:10		*02:01
*02:02
*02:03
*02:04		*03:01
*03:02
*03:03		*04:01

HLA-DPB1 Alleles

HLA-DPB1
*01*01:01
*02*02:01
*02:02
*03*03:01
*04*04:01
*04:02
*05*05:01
*06*06:01
*07*07:01
*08*08:01
*09*09:01
*10*10:01
DPB1*11:01 - DPB1*129:01

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, [1] 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. [2]

Previous NamesCurrent Names
DPB1*0102DPB1*100:01
DPB1*0203DPB1*101:01
DPB1*0302DPB1*102:01
DPB1*0403DPB1*103:01
DPB1*0502DPB1*104:01
DPB1*0602DPB1*105:01
DPB1*0802DPB1*106:01
DPB1*0902DPB1*107:01
DPB1*1002DPB1*108:01
DPB1*1102DPB1*109:01
DPB1*1302DPB1*110:01
DPB1*1402DPB1*111:01
DPB1*1502DPB1*112:01
DPB1*1602DPB1*113:01
DPB1*1702DPB1*114:01
DPB1*1802DPB1*115:01
DPB1*1902DPB1*116:01
DPB1*2002DPB1*117:01
DPB1*2102DPB1*118:01
DPB1*2202DPB1*119:01
DPB1*2302NDPB1*120:01N
DPB1*2402DPB1*121:01
DPB1*2502DPB1*122:01
DPB1*2602DPB1*123:01
DPB1*2702DPB1*124:01
DPB1*2802DPB1*125:01

To aid in migration of data to the new nomenclature the WHO Nomenclature Committee for Factors of the HLA System has provided the IMGT/HLA Nomenclature Conversion Tool Archived 2012-08-04 at the Wayback Machine . 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:

DPB1*126:01
DPB1*127:01
DPB1*128:01
DPB1*129:01

Common DP Haplotypes

HLA-DPA1*01:03/DPB1*04:01 (DP401)
HLA-DPA1*01:03/DPB1*04:02 (DP402)

Related Research Articles

<span class="mw-page-title-main">Major histocompatibility complex</span> Cell surface proteins, part of the acquired immune system

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 called MHC molecules.

<span class="mw-page-title-main">Human leukocyte antigen</span> Genes on human chromosome 6

The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

<span class="mw-page-title-main">HLA-DR</span> Subclass of HLA-D antigens that consist of alpha and beta chains

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 and peptide, generally between 9 and 30 amino acids in length, constitutes a ligand for the T-cell receptor (TCR). HLA were originally defined as cell surface antigens that mediate graft-versus-host disease. Identification of these antigens has led to greater success and longevity in organ transplant.

<span class="mw-page-title-main">MHC class II</span> Protein of the immune system

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, macrophages, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.

<span class="mw-page-title-main">HLA-DQ</span> Cell surface receptor protein found on antigen-presenting cells.

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 chromosome band 6p21.3. Both α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 isoforms of DQ. The DQ loci are in close genetic linkage to HLA-DR, and less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.

HLA DR3-DQ2 is a double serotype that specifically recognizes cells from individuals who carry a multigene HLA DR, DQ haplotype. Certain HLA DR and DQ genes have known involvement in autoimmune diseases. DR3-DQ2, a multigene haplotype, stands out in prominence because it is a factor in several prominent diseases, namely coeliac disease and juvenile diabetes. In coeliac disease, the DR3-DQ2 haplotype is associated with highest risk for disease in first degree relatives, highest risk is conferred by DQA1*0501:DQB1*0201 homozygotes and semihomozygotes of DQ2, and represents the overwhelming majority of risk. HLA DR3-DQ2 encodes DQ2.5cis isoform of HLA-DQ, this isoform is described frequently as 'the DQ2 isoform', but in actuality there are two major DQ2 isoform. The DQ2.5 isoform, however, is many times more frequently associated with autoimmune disease, and as a result to contribution of DQ2.2 is often ignored.

<span class="mw-page-title-main">HLA-DQ2</span> Human leukocyte antigen serotype

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

<span class="mw-page-title-main">HLA-DQ4</span>

HLA-DQ4 (DQ4) is a serotype subgroup within HLA-DQ(DQ) serotypes. The serotype is determined by the antibody recognition of β4 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ4 are encoded by the HLA-DQB1*04 allele group. This group currently contains 2 common alleles, DQB1*0401 and DQB1*0402. HLA-DQ4 and HLA-DQB1*04 are almost synonymous in meaning. DQ4 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ4.3 and DQ4.4, are also encoded by the DQA1*0303 and DQA1*0401 genes, respectively.

<span class="mw-page-title-main">HLA-DQ6</span>

HLA-DQ6 (DQ6) is a human leukocyte antigen serotype within HLA-DQ (DQ) serotype group. The serotype is determined by the antibody recognition of β6 subset of DQ β-chains. The β-chain of DQ isoforms are encoded by HLA-DQB1 locus and DQ6 are encoded by the HLA-DQB1*06 allele group. This group currently contains many common alleles, DQB1*0602 is the most common. HLA-DQ6 and DQB1*06 are almost synonymous in meaning. DQ6 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 α-chains. There are many haplotypes of DQ6.

<span class="mw-page-title-main">HLA-DQ7</span>

HLA-DQ7 (DQ7) is an HLA-DQ serotype that recognizes the common HLA DQB1*0301 and the less common HLA DQB1*0304 gene products. DQ7 is a form of 'split antigen' of the broad antigen group DQ3 which also contains DQ8 and DQ9.

<span class="mw-page-title-main">HLA-DQ1</span> Serotype that covers a broad range of HLA-DQ haplotypes.

HLA-DQ1 is a serotype that covers a broad range of HLA-DQ haplotypes. Historically it was identified as a DR-like alpha chain called DC1; later, it was among 3 types DQw1, DQw2 and DQw3. Of these three serotyping specificities only DQw1 recognized DQ alpha chain. The serotype is positive in individuals who bear the DQA1*01 alleles. The most frequently found within this group are: DQA1*0101, *0102, *0103, and *0104. In the illustration on the right, DQ1 serotyping antibodies recognizes the DQ α (magenta), where antibodies to DQA1* gene products bind variable regions close to the peptide binding pocket.

<span class="mw-page-title-main">HLA-DR52</span>

HLA-DR52 is an HLA-DR serotype that recognizes gene products of HLA-DRB3 locus. Three allele groups can produce 35 isoforms.

<span class="mw-page-title-main">HLA-DR51</span>

HLA-DR51 is a HLA-DR serotype that recognizes the antigens encoded by the minor DR locus HLA-DRB5.

<span class="mw-page-title-main">HLA-DR7</span>

HLA-DR7 (DR7) is a HLA-DR serotype that recognizes the DRB1*0701 to *0705 gene products.

<span class="mw-page-title-main">HLA-A*02</span> Human leukocyte antigen serotype within the HLA-A serotype group

HLA-A*02 (A*02) is a human leukocyte antigen serotype within the HLA-A serotype group. The serotype is determined by the antibody recognition of the α2 domain of the HLA-A α-chain. For A*02, the α chain is encoded by the HLA-A*02 gene and the β chain is encoded by the B2M locus. In 2010 the World Health Organization Naming Committee for Factors of the HLA System revised the nomenclature for HLAs. Before this revision, HLA-A*02 was also referred to as HLA-A2, HLA-A02, and HLA-A*2.

<span class="mw-page-title-main">HLA-A32</span> Human leukocyte antigen serotype

HLA-A32 (A32) is a human leukocyte antigen serotype within HLA-A serotype group. The serotype is determined by the antibody recognition of α32 subset of HLA-A α-chains. For A32, the alpha "A" chain are encoded by the HLA-A*32 allele group and the β-chain are encoded by B2M locus. This group currently is dominated by A*3201. A32 and A*32 are almost synonymous in meaning. A32 is a split antigen of the broad antigen serotype A19. A32 is a sister serotype of A29, A30, A31, A33, and A74.

<span class="mw-page-title-main">HLA-DQB1</span> Protein-coding gene in the species Homo sapiens

Major histocompatibility complex, class II, DQ beta 1, also known as HLA-DQB1, is a human gene and also denotes the genetic locus that contains this gene. The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.

<span class="mw-page-title-main">Major histocompatibility complex, class II, DQ alpha 1</span> Protein-coding gene in the species Homo sapiens

Major histocompatibility complex, class II, DQ alpha 1, also known as HLA-DQA1, is a human gene present on short arm of chromosome 6 (6p21.3) and also denotes the genetic locus which contains this gene. The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.

<span class="mw-page-title-main">HLA-DPB1</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene.

Human leukocyte antigens (HLA) began as a list of antigens identified as a result of transplant rejection. The antigens were initially identified by categorizing and performing massive statistical analyses on interactions between blood types. This process is based upon the principle of serotypes. HLA are not typical antigens, like those found on surface of infectious agents. HLAs are alloantigens, they vary from individual to individual as a result of genetic differences. An organ called the thymus is responsible for ensuring that any T-cells that attack self proteins are not allowed to live. In essence, every individual's immune system is tuned to the specific set of HLA and self proteins produced by that individual; where this goes awry is when tissues are transferred to another person. Since individuals almost always have different "banks" of HLAs, the immune system of the recipient recognizes the transplanted tissue as non-self and destroys the foreign tissue, leading to transplant rejection. It was through the realization of this that HLAs were discovered.

References

  1. ↑ Marsh, S. G. E., Albert, E. D., Bodmer, W. F., Bontrop, R. E., Dupont, B., Erlich, H. A., Fernández-Viña, M., Geraghty, D. E., Holdsworth, R., Hurley, C. K., Lau, M., Lee, K. W., Mach, B., Maiers, M., Mayr, W. R., Müller, C. R., Parham, P., Petersdorf, E. W., Sasazuki, T., Strominger, J. L., Svejgaard, A., Terasaki, P. I., Tiercy, J. M., Trowsdale, J. (2010). "Nomenclature for factors of the HLA system, 2010". Tissue Antigens. 75 (4): 291–455. doi:10.1111/j.1399-0039.2010.01466.x. PMC   2848993 . PMID   20356336.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ↑ ftp://ftp.ebi.ac.uk/pub/databases/imgt/mhc/hla/Nomenclature_2009.txt
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