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the 4th letter of the Roman alphabet (同)d
the 8th letter of the Roman alphabet (同)h

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deuteriumの化学記号
hydrogenの化学記号
鉛筆の硬度 / 《俗》heroin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/01 14:30:26」(JST)

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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.

Structure, Functions, Genetics

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

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
DPB111:01 - DPB1129:01

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]^[3]

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

DPB1126:01 DPB1127:01 DPB1128:01 DPB1129:01

Common DP Haplotypes

HLA-DPA101:03/DPB104:01 (DP401)
HLA-DPA101:03/DPB104:02 (DP402)

External links

Nomenclature of HLA Alleles
The IMGT/HLA Database - HLA Dictionary.
HLA Allele and Haplotype Frequency Database

References

^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2848993/.
^ ftp://ftp.ebi.ac.uk/pub/databases/imgt/mhc/hla/Nomenclature_2009.txt
^ http://hlatype.com/hla-dpb1-old-and-new-nomenclature-conversion/

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 造血細胞移植のためのドナー選定 donor selection for hematopoietic cell transplantation
2. 慢性骨髄性白血病における造血細胞移植 hematopoietic cell transplantation in chronic myeloid leukemia
3. 慢性ベリリウム症（ベリリウム症） chronic beryllium disease berylliosis
4. 若年性特発性関節炎：疫学と免疫病態学 juvenile idiopathic arthritis epidemiology and immunopathogenesis
5. 移植免疫 transplantation immunobiology

English Journal

Altered expression levels of HLA class Ⅱ and costimulatory molecules on circulating monocytes from patients with cervical intraepithelial neoplasia and squamous cervical cancer.

Feng T, Zhou JH, Liu J, Ye F, Lu W, Xie X.SourceDepartment of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, P.R. China.
Molecular medicine reports.Mol Med Report.2012 Dec;6(6):1301-4. doi: 10.3892/mmr.2012.1068. Epub 2012 Sep 10.
The aim of this study was to investigate the role of the cell surface expression levels of HLA class I and II molecules, the costimulatory molecules CD80/B7-1 and CD86/B7-2, and the adhesion molecules CD54 and CD58 during cervical carcinogenesis. The expression le
PMID 22965188

HLA-DP gene polymorphisms and hepatitis B infection in the Japanese population.

Migita K, Abiru S, Ohtani M, Jiuchi Y, Maeda Y, Bae SK, Bekki S, Hashimoto S, Yesmembetov K, Nagaoka S, Nakamura M, Komori A, Ichikawa T, Nakao K, Yatsuhashi H, Ishibashi H, Yasunami M.SourceClinical Research Center, NHO Nagasaki Medical Center, Omura, Japan. Electronic address: migita@nmc.hosp.go.jp.
Translational research : the journal of laboratory and clinical medicine.Transl Res.2012 Dec;160(6):443-4. doi: 10.1016/j.trsl.2012.06.003. Epub 2012 Jun 28.
PMID 22749777

Japanese Journal

ゲノムワイド関連解析による慢性B型肝炎疾患感受性遺伝子の同定 (特集ウイルス肝炎の病態解明と治療の進歩)

松田浩一,中村祐輔
最新医学 65(9), 1863-1869, 2010-09
NAID 40017296884

アジア人における慢性B型肝炎に関する遺伝子多型 (AYUMI HLAと疾患--最新トピックス)

松田浩一,中村祐輔
医学のあゆみ 233(13), 1193-1198, 2010-06-26
NAID 40017154194

Related Pictures

★リンクテーブル★

リンク元	「主要組織適合複合体」
拡張検索	「HLA-DP antigen」
関連記事	「D」「HL」「DP」「H」「HLA」

「主要組織適合複合体」

	MHC class II, DP (heterodimer)
	-
Protein type	cell surface receptor
Function	Immune recognition and; antigen presentation
	-

　　[★]

英: major histocompatibility complex, MHC
同: ヒト白血球抗原 human leucocyte antigen, HLA　←　LHA/MHCの疾患との遺伝的関係についてはここを参照、MHC分子、主要組織適合遺伝子複合体
関

MHCのクラスと特徴 (出典不明)

	MHC class I	*MHC class II
MHC発現組織	全ての有核細胞(×赤血球)	CD4陽性T細胞
		CD8陽性T細胞
		抗原提示細胞(マクロファージ、樹状細胞、ランゲルハンス細胞、クッパー細胞、ミクログリア、B細胞)
抗原認識するリンパ球	Tc細胞	Th細胞
ドメイン構造	α鎖(α1,2,3を持つ分子)とβ2-microgloblin	α鎖(α1,α2を持つ分子)とβ鎖(β1,β2を持つ分子)
遺伝子座	HLA-A,B,C,	HLA-DP,DQ,DR
提示されるペプチド	内在抗原	外来抗原
抗原ペプチドの長さ	9残基	12-30残基
抗原ペプチドとMHCとの相互作用部位	2残基	3(免疫学授業プリント) 4(IMM.131)

MHC分子の発現 (IMM.136)

		MHC class I	MHC class II
リンパ組織	T細胞	＋＋＋	＋
	B細胞	＋＋＋	＋＋＋
	マクロファージ	＋＋＋	＋＋
	樹状細胞	＋＋＋	＋＋＋
	胸腺上皮細胞	＋	＋＋＋
有核細胞	好中球	＋＋＋	－
	肝細胞	＋	－
	腎臓	＋	－
	脳	＋	－
無核細胞	赤血球	－	－

　　主要組織適合遺伝子複合体
　　　　移植抗原として発見された抗原系
　　　　応答免疫(抗原提示)に関与する
　　ヒト(HLA complex) human leucocyte antigen
　　　HLA
　　　ドメイン構造
　　　　クラスI		A	B	C
　　　　クラスII	DP	DQ	DR
　　　多型性がある
　　　12種類のHLAを発現(父由来、母由来)
　　マウス(H2 complex) Histcompatibility-2
　　　ドメイン構造
　　　　クラスI		K	D
　　　　クラスII	A	E
　　MHCの歴史
　　　G.Snell		マウスH2が移植の正否を左右する
　　　J.Dausset		HLAが抗原
　　　B.Benaceraf	MHC遺伝子を明らかにし、MHCが免疫応答に関与していることを証明

(1)分子構造

　クラスI　H鎖　β2-microglobulin
　クラスII　α鎖　β鎖
　細胞外領域　膜貫通領域　細胞内領域
　ドメイン
　Igスーパーファミリー
　クリスタログラフィー　crystallography

(2) MHC分子の生合成

　抗原処理
　抗原提示
　クラスI (proteasome TAP)
　　クラスI抗原提示(内在性抗原)
　　①ほとんどの細胞が提示
　　　ただし赤血球には発現していない
　　②細胞内：内在抗原をプロテアソーム(LMP複合体)が分子切断→ERに移動
　　③ERI TAPトランスポーターによりER内に移動
　　　クラスI+ペプチド複合体形成
　　④細胞表面に移動
　　⑤Tc(CD8+ T細胞)細胞が認識：標的細胞を障害
　クラスII (Ii=invariant chain, HLA-DM)
　　クラスII抗原提示(外来抗原)
　　①抗原提示細胞：貪食、飲食による取り込み
　　②ファゴリソゾーム：ペプチドに分解
　　③小胞体(ER)：(MHC class II + Ii鎖)複合
　　④ファゴリソゾーム：HLA-DMがIi鎖を解離
　　　ペプチドを提示→(MHC class II + ペプチド)複合体
　　⑤細胞表面に移動
　　⑥Th(CD4+T)細胞が認識

(3) MHC遺伝子

MHC遺伝子座

クラスI：HLA-A,HLA-B,HLA-C(古典的)

→全ての有核細胞が発現

　　　最近、E,F,Gが発見された→E,FはT細胞、Gは胎盤トロホブラストが発現(妊娠免疫に重要)

クラスII：HLA-DP,HLA-DQ,HLA-DR

→限定された細胞が発現(マクロファージ、樹状細胞、ランゲルハンス細胞、クッパー細胞)

亜領域A1,A2,およびB1,B2を有し、いずれかしか発現しない。ちなみに、Aはα鎖、Bはβ鎖をコードしている。

HLA-DM、LMP、TAP遺伝子座がDP-DQ間に発現していることが明らかとなった

クラスIII：補体成分：C2,C4,Bf

　　　　　　　　サイトカイン：TNPet,C,
　　　　　　　　酵素：21-hydroxylase
　クラス(領域　亜領域)
　遺伝的多塑性　polymorphism
　対立遺伝子頻度

-MHC

同: 主要組織適合遺伝子複合体

「HLA-DP antigen」

　　[★]

HLA-DP抗原

関: HLA-DP

「D」

　　[★]

アスパラギン酸
ジヒドロウリジン
遠位の distal,
うつ病 depression
下行結腸 descending colon(大腸内視鏡検査の結果を記載するときに用いる)

「HL」

　　[★]

「DP」

　　[★]

「H」

　　[★]

「HLA」

　　[★] ヒト白血球抗原 human leukocyte antigen

[0] 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2848993/.

[1] tp://ftp.ebi.ac.uk/pub/databases/imgt/mhc/hla/Nomenclature_2009.txt

[2] ttp://hlatype.com/hla-dpb1-old-and-new-nomenclature-conversion/

匿名

検索

案内

案内

HLA-DP