Cutting Edge: Coding Single Nucleotide Polymorphisms of Endoplasmic Reticulum Aminopeptidase 1 Can Affect Antigenic Peptide Generation In Vitro by Influencing Basic Enzymatic Properties of the Enzyme

被引：116

作者：

Evnouchidou, Irini ^{[1
]}

Kamal, Ram P. ^{[2
]}

Seregin, Sergey S. ^{[2
]}

Goto, Yoshikuni ^{[3
]}

Tsujimoto, Masafumi ^{[3
]}

Hattori, Akira ^{[4
]}

Voulgari, Paraskevi V. ^{[5
]}

Drosos, Alexandros A. ^{[5
]}

Amalfitano, Andrea ^{[2
]}

York, Ian A. ^{[2
]}

Stratikos, Efstratios ^{[1
]}

机构：

[1] Natl Ctr Sci Res Demokritos, Prot Chem Lab, Athens 15310, Greece

[2] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA

[3] Teikyo Heisei Univ, Fac Pharmaceut Sci, Chiba 2900193, Japan

[4] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Syst Chemotherapy & Mol Sci, Sakyo Ku, Kyoto 6068501, Japan

[5] Univ Ioannina, Sch Med, Dept Internal Med, Rheumatol Clin, GR-45110 Ioannina, Greece

来源：

JOURNAL OF IMMUNOLOGY | 2011年 / 186卷 / 04期

关键词：

PRESENTED PEPTIDES; ER AMINOPEPTIDASE; TRIMS PRECURSORS; MHC; ERAP1; ASSOCIATION; MOLECULES; MECHANISM; ERAAP;

D O I：

10.4049/jimmunol.1003337

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

ER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the antigenic peptide repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis of autoimmunity and ERAP1-mediated Ag processing. To investigate this possibility, we analyzed the effect that disease-linked SNPs have on Ag processing by ERAP1 in vitro. Michaelis-Menten analysis revealed that the presence of SNPs affects the Michaelis constant and turnover number of the enzyme. Strikingly, specific ERAP1 allele-substrate combinations deviate from standard Michaelis-Menten behavior, demonstrating substrate-inhibition kinetics; to our knowledge, this phenomenon has not been described for this enzyme. Cell-based Ag-presentation analysis was consistent with changes in the substrate inhibition constant K-i, further supporting that ERAP1 allelic composition may affect Ag processing in vivo. We propose that these phenomena should be taken into account when evaluating the possible link between Ag processing and autoimmunity. The Journal of Immunology, 2011, 186: 1909-1913.

引用

页码：1909 / 1913

页数：5

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