The specificity of trimming of MHC class I-presented peptides in the endoplasmic reticulum.
The specificity of trimming of MHC class I-presented peptides in the endoplasmic reticulum.
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DOI：
10.4049/jimmunol.0803663
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发表时间：
2009-11-01
期刊：
影响因子：
--
通讯作者：
Rock KL
中科院分区：
文献类型：
--
作者：
Hearn A;York IA;Rock KL
内质网 (ER) 中的氨基肽酶可以裂解抗原肽，从而创建或破坏 MHC I 类呈递的表位。然而，这种修剪过程的特异性，特别是主要 ER 氨肽酶 ERAP1 的特异性，目前尚不清楚。这个问题很重要，因为肽修剪会影响 CD8 T 细胞反应的幅度和特异性。通过系统地改变无细胞生化系统和完整细胞中肽的 N 端侧翼序列，我们总体上阐明了 ERAP1 和 ER 修剪的特异性。 ERAP1 可以在表位前体 N 末端的许多氨基酸后进行切割，但切割速度明显不同。纯化的 ERAP1 所观察到的特异性与完整细胞 ER 中表位修剪和呈递所观察到的特异性相似。我们以独立于表位核心序列的方式定义有利于或不利的抗原呈递的 N 端序列。当分析已知呈现的肽的数据库时，发现通常在表位的 N 端侧翼序列中过度呈现用于修剪模型肽前体的残基。这些数据定义了抗原加工特异性的关键决定因素。
Aminopeptidases in the endoplasmic reticulum (ER) can cleave antigenic peptides and in so doing either create or destroy MHC class I-presented epitopes. However the specificity of this trimming process overall and of the major ER aminopeptidase ERAP1 in particular is not well understood. This issue is important because peptide trimming influences the magnitude and specificity of CD8 T cell responses. By systematically varying the N-terminal flanking sequences of peptides in a cell free biochemical system and in intact cells, we elucidated the specificity of ERAP1 and of ER trimming overall. ERAP1 can cleave after many amino acids on the N-terminus of epitope precursors but does so at markedly different rates. The specificity seen with purified ERAP1 is similar to that observed for trimming and presentation of epitopes in the ER of intact cells. We define N-terminal sequences that are favorable or unfavorable for antigen presentation in ways that are independent from the epitopes core sequence. When databases of known presented peptides were analyzed, the residues that were preferred for the trimming of model peptide precursors were found to be overrepresented in N-terminal flanking sequences of epitopes generally. These data define key determinants in the specificity of antigen processing.
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DOI：
10.1084/jem.190.9.1227
发表时间：
1999-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lauvau G;Kakimi K;Niedermann G;Ostankovitch M;Yotnda P;Firat H;Chisari FV;van Endert PM
通讯作者：
van Endert PM
影响因子：
4.8
作者：
Beninga, J;Rock, KL;Goldberg, AL
通讯作者：
Goldberg, AL
影响因子：
--
作者：
BERGER, AE;DAVIS, JE;CRESSWELL, P
通讯作者：
CRESSWELL, P
影响因子：
32.4
作者：
Porgador, A;Yewdell, JW;Germain, RN
通讯作者：
Germain, RN
影响因子：
11.4
作者：
Cascio, P;Hilton, C;Goldberg, AL
通讯作者：
Goldberg, AL