HLA-DP Totally Explained

Everything about Hla-dp totally explained

major histocompatibility complex, class II, DP
Structure
Type	Cell surface receptor
Quartenary	αβ-heterodimer
MMDB	None available
Identifiers	alpha 1
Symbol(s)	HLA-DPA1
Entrez	3113
OMIM	142880
RefSeq	NM_003355 ?
UniProt	P20036
Identifiers	beta 1
Symbol(s)	HLA-DPB1
Entrez	4940
OMIM	142858
RefSeq	NM_002121 ?
UniProt	P04440
Shared data
Locus	chr.6 6p21.31

HLA-DP is a protein/peptide-antigen receptor and graft-versus-host disease antigen that's 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.

Structure, Functions, Genetics

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, 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 (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 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 wasn't as actively selected in the evolution of Super B8.

Understanding the Heterdimeric DP Isoforms

Result: 2 Cis, α^mβ^m & α^pβ^p, isoforms and 2 trans,α^mβ^p & α^pβ^m.

	allele	(m)	(p)
HLA		DPB1
DPA1	(m)	α^mβ^m (Cis ^m)	α^mβ^p (Trans)
DPA1	(p)	α^p_β^m (Trans)	α^pβ^p (Cis ^p)

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
- 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)

Further Information

Get more info on 'Hla-dp'.

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