دورية أكاديمية
Distinct modulation of cellular immunopeptidome by the allosteric regulatory site of ER aminopeptidase 1.
العنوان: | Distinct modulation of cellular immunopeptidome by the allosteric regulatory site of ER aminopeptidase 1. |
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المؤلفون: | Temponeras I; National Centre for Scientific Research Demokritos, Agia Paraskevi, Greece.; Department of Pharmacy, University of Patras, Patra, Greece., Samiotaki M; Biomedical Sciences Research Center 'Alexander Fleming,', Institute for Bioinnovation, Vari, Greece., Koumantou D; National Centre for Scientific Research Demokritos, Agia Paraskevi, Greece., Nikopaschou M; National Centre for Scientific Research Demokritos, Agia Paraskevi, Greece.; Department of Chemistry, National and Kapodistrian University of Athens, Zografou, Greece., Kuiper JJW; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Panayotou G; Biomedical Sciences Research Center 'Alexander Fleming,', Institute for Bioinnovation, Vari, Greece., Stratikos E; National Centre for Scientific Research Demokritos, Agia Paraskevi, Greece.; Department of Chemistry, National and Kapodistrian University of Athens, Zografou, Greece. |
المصدر: | European journal of immunology [Eur J Immunol] 2023 Aug; Vol. 53 (8), pp. e2350449. Date of Electronic Publication: 2023 May 15. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 1273201 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-4141 (Electronic) Linking ISSN: 00142980 NLM ISO Abbreviation: Eur J Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2005->: Weinheim : Wiley-VCH Original Publication: Weinheim, Verlag Chemie GmbH. |
مواضيع طبية MeSH: | Aminopeptidases*/genetics , Peptides*, Humans ; Antigen Presentation ; Antigens ; Minor Histocompatibility Antigens/genetics ; Minor Histocompatibility Antigens/metabolism |
مستخلص: | ER aminopeptidase 1 (ERAP1) is an ER-resident aminopeptidase that excises N-terminal residues of peptides that then bind onto Major Histocompatibility Complex I molecules (MHC-I) and indirectly modulates adaptive immune responses. ERAP1 contains an allosteric regulatory site that accommodates the C-terminus of at least some peptide substrates, raising questions about its exact influence on antigen presentation and the potential of allosteric inhibition for cancer immunotherapy. We used an inhibitor that targets this regulatory site to study its effect on the immunopeptidome of a human cancer cell line. The immunopeptidomes of allosterically inhibited and ERAP1 KO cells contain high-affinity peptides with sequence motifs consistent with the cellular HLA class I haplotypes but are strikingly different in peptide composition. Compared to KO cells, allosteric inhibition did not affect the length distribution of peptides and skewed the peptide repertoire both in terms of sequence motifs and HLA allele utilization, indicating significant mechanistic differences between the two ways of disrupting ERAP1 function. These findings suggest that the regulatory site of ERAP1 plays distinct roles in antigenic peptide selection, which should be taken into consideration when designing therapeutic interventions targeting the cancer immunopeptidome. (© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.) |
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معلومات مُعتمدة: | 954992-CAPSTONE-H2020-MSCA-ITN-2020 United Kingdom MCCC_ Marie Curie |
فهرسة مساهمة: | Keywords: Major Histocompatibility Molecules class I; allosteric inhibitor; autoimmunity; cancer immunotherapy; immunopeptidome |
المشرفين على المادة: | EC 3.4.11.- (Aminopeptidases) 0 (Peptides) 0 (Antigens) 0 (Minor Histocompatibility Antigens) EC 3.4.11.- (ERAP1 protein, human) |
تواريخ الأحداث: | Date Created: 20230503 Date Completed: 20230814 Latest Revision: 20230815 |
رمز التحديث: | 20231215 |
DOI: | 10.1002/eji.202350449 |
PMID: | 37134263 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1521-4141 |
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DOI: | 10.1002/eji.202350449 |