The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules

Hammer GE; Gonzalez F; Champsaur M; Cado D; Shastri N

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The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules

机译：氨基肽酶ERAAP决定主要组织相容性复合物I类分子显示的肽库

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Major histocompatibility complex (MHC) class I molecules present thousands of peptides to allow CD8(+) T cells to detect abnormal intracellular proteins. The antigen-processing pathway for generating peptides begins in the cytoplasm, and the MHC molecules are loaded in the endoplasmic reticulum. However, the nature of peptide pool in the endoplasmic reticulum and the proteolytic events that occur in this compartment are unclear. We addressed these issues by generating mice lacking the endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP). We found that loss of ERAAP disrupted the generation of naturally processed peptides in the endoplasmic reticulum, decreased the stability of peptide-MHC class I complexes and diminished CD8(+) T cell responses. Thus, trimming of antigenic peptides by ERAAP in the endoplasmic reticulum is essential for the generation of the normal repertoire of processed peptides.

机译：主要的组织相容性复合体（MHC）I类分子可提供数千种肽，以使CD8（+）T细胞能够检测异常的细胞内蛋白。用于产生肽的抗原加工途径始于细胞质，并且MHC分子被装载在内质网中。但是，内质网中肽库的性质和在该区室中发生的蛋白水解事件尚不清楚。我们通过产生缺乏与抗原加工（ERAAP）相关的内质网氨基肽酶的小鼠来解决这些问题。我们发现丢失ERAAP破坏了内质网中天然加工的肽的生成，降低了肽-MHC I类复合物的稳定性，并减少了CD8（+）T细胞反应。因此，在内质网中通过ERAAP修整抗原肽对于生成正常的加工肽库至关重要。

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《Nature immunology》 |2006年第1期|共10页
作者
Hammer GE; Gonzalez F; Champsaur M; Cado D; Shastri N;
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正文语种 eng
中图分类基础医学;
关键词
LEUCYL-SPECIFIC AMINOPEPTIDASE; EPITOPE PRECURSOR PEPTIDES; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; EXPRESSION CLONING; PRESENTED PEPTIDES; CELLS; GENERATION; IDENTIFICATION; TAPASIN;

机译：特定于肽的氨基肽酶;表皮前体肽;内质网;抗原表达;表达克隆;表达的肽;细胞;生成;鉴定;酪蛋白;

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专利

1. The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules [J] . Hammer GE, Gonzalez F, Champsaur M, Nature immunology . 2006,第1期

机译：氨基肽酶ERAAP决定主要组织相容性复合物I类分子显示的肽库
2. Modulation of major histocompatibility complex Class I molecules and major histocompatibility complex-bound immunogenic peptides induced by interferon-alpha and interferon-gamma treatment of human glioblastoma multiforme. [J] . Yang I, Kremen TJ, Giovannone AJ, Journal of neurosurgery. . 2004,第2期

机译：干扰素-α和干扰素-γ治疗人成胶质细胞瘤的主要组织相容性复合物I类分子和主要组织相容性复合物结合的免疫原性肽的调节。
3. IDENTIFICATION FROM A PHAGE DISPLAY LIBRARY OF PEPTIDES THAT BIND TO TOXIC SHOCK SYNDROME TOXIN-1 AND THAT INHIBIT ITS BINDING TO MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS II MOLECULES [J] . Sato A, Ida N, Fukuyama M, Biochemistry . 1996,第32期

机译：从肽的噬菌体展示库中鉴定出与毒性休克综合症毒素1结合并抑制其与主要组织相容性复合物（MHC）II类分子结合的肽
4. Invariant chain regulates the major histocompatibility complex class II peptide repertoire of cell-based cancer vaccines. [C] . Olesya Y. Chornoguz, Lydia Grmai, Alexei Gapeev, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2010

机译：不变链调节细胞基癌症疫苗的主要组织相容性复合体II类肽曲目。
5. Generation of soluble class II major histocompatibility complex molecules and analysis of histidine participation in enhanced peptide binding at low pH. [D] . Wettstein, Daniel Albert. 1993

机译：可溶性II类主要组织相容性复合物分子的产生以及在低pH下组氨酸参与增强肽结合的分析。
6. P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities [O] . 1993

机译：P58分子是人类自然杀伤（NK）细胞中主要组织相容性复合体（MHC）I类分子的推定受体。抗p58抗体可重构显示不同特异性的NK克隆中MHC I类保护的细胞
7. P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities [O] . 1993

机译：P58分子是人类自然杀伤（NK）细胞中主要组织相容性复合体（MHC）I类分子的推定受体。抗p58抗体可重构显示不同特异性的NK克隆中MHC I类保护的细胞
8. Small Peptide (CEL-1000) Derived from the Beta-Chain of the Human Major Histocompatibility Complex Class II Molecule Induces Complete Protection Against Malaria in an Antigen-Independent Manner [R] . Charoenvit, Y. , Brice, G. T. , Bacon, D. , 2004

机译：源自人类主要组织相容性复合物II类分子的β-链的小肽（CEL-1000）以抗原非依赖性方式诱导针对疟疾的完全保护

The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules

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