HLA-DP

heteropolypeptide
heteropolymer = MHC class II, DP
polymer_type = heterodimer
protein_type = cell surface receptor
function = Immune recognition and
antigen presentation


image_source = DP binding pocket with ligand
SubunitCount = 2
subunit1 = α
gene1 = HLA-DPA1
locus1 = Chromosome 6p21.31
subunit2 = β
gene2 = HLA-DPB1
locus2 = 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.

tructure, Functions, Genetics

tructure

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, a 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 DQ 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 suppressor 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 Heterdimeric 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

DPA1
*01
**0103
**0104
**0105
**0106
**0107
**0108
**0109
*02
**0201
**0202
**0203
*03
**0301
**0302
**0303
*0401 DPB1
*01
**0101
**0102
*02
**0201 early onset myasthenia gravis [cite journal | author = Horiki T, Inoko H, Moriuchi J, Ichikawa Y, Arimori S | title = Combinations of HLA-DPB1 and HLA-DQB1 alleles determine susceptibility to early-onset myasthenia gravis in Japan. | journal = Autoimmunity | volume = 19 | issue = 1 | pages = 49–54 | year = 1994 | pmid = 7749041]
**0202
**0203
*03
*04
**0401
**0402
**0403
*05
**0501
**0502
*06
**0501
**0502
*06
**0501
**0502
*06
**0501
**0502
*06
**0501
**0502
*08
**0801
**0802
*09
**0901
**0902
*10
**1001
**1002
*11
**1101
**1102
*13
**1301
**1302
*14
**1401
**1402
*15
**1501
**1502
*16
**1601
**1602
*17
**1701
**1702
*18
**1801
**1802
*19
**1901
**1902
*20
**2001
**2002
*21
*22
*23
*24
*25
*26
**2601
**2602
*27 - *99

Haplotypes

HLA-DPA1*0103/DPB1*0401 (DP401)HLA-DPA1*0103/DPB1*0402 (DP402)

External links

* [http://tech.groups.yahoo.com/group/DNAanthro/ Molecular Anthropology Yahoo Group]

* [http://www.allelefrequencies.net HLA Allele and Haplotype Frequency Database]

References


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