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Comprehensive mapping of identical sequences across human proteins emphasizes the widespread issue of shared epitopes in self-antigens.

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Τίτλος: Comprehensive mapping of identical sequences across human proteins emphasizes the widespread issue of shared epitopes in self-antigens.
Συγγραφείς: Kellermann G; Telomium SAS, Ivry-sur-Seine 94200, France., Croce O; Université Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut Hospitalo-Universitaire (IHU) RespirERA, Fédération Hospitalo-Universitaire (FHU) OncoAge, Nice, France., Mograbi B; Université Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut Hospitalo-Universitaire (IHU) RespirERA, Fédération Hospitalo-Universitaire (FHU) OncoAge, Nice, France., Hofman P; Université Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut Hospitalo-Universitaire (IHU) RespirERA, Fédération Hospitalo-Universitaire (FHU) OncoAge, Nice, France.; Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire (CHU) de Nice, IHU RespirERA, FHU OncoAge, Biobank BB-0033-00025, Nice, France., Brest P; Université Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut Hospitalo-Universitaire (IHU) RespirERA, Fédération Hospitalo-Universitaire (FHU) OncoAge, Nice, France.
Πηγή: NAR genomics and bioinformatics [NAR Genom Bioinform] 2026 Jun 22; Vol. 8 (2), pp. lqag060. Date of Electronic Publication: 2026 Jun 22 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Oxford University Press Country of Publication: England NLM ID: 101756213 Publication Model: eCollection Cited Medium: Internet ISSN: 2631-9268 (Electronic) Linking ISSN: 26319268 NLM ISO Abbreviation: NAR Genom Bioinform Subsets: MEDLINE
Imprint Name(s): Original Publication: [Oxford] : Oxford University Press, [2019]-
Ιατρικοί όροι (MeSH): Autoantigens*/immunology , Autoantigens*/chemistry , Autoantigens*/genetics , Epitopes*/immunology , Epitopes*/chemistry , Epitopes*/genetics , Epitope Mapping*/methods, Antigens, Neoplasm/immunology ; Antigens, Neoplasm/chemistry ; Antigens, Neoplasm/genetics ; Humans ; Animals ; Mice ; Amino Acid Sequence ; Immunoinformatics ; Software
Περίληψη: Shared epitopes pose safety and efficacy issues for T-cell immunotherapy. To characterize the extent of this problem, we performed a computational analysis establishing a complete atlas of shared identical sequences across the human and murine proteomes. Unlike bacterial or viral antigens, self-antigens, including tumor-associated antigens (TAAs), frequently contain sequences of sufficient length to generate identical epitopes in other self-proteins. Epitopes from these shared sequences can theoretically reduce target specificity, confound immunomonitoring studies, and contribute to pre-existing immune tolerance toward TAAs. Notably, a subset of TAAs identified in this atlas is free of this drawback, providing a new criterion for antigen prioritization in cancer immunotherapy. To facilitate the detection of shared sequences, a web server has been made available at https://epitopemapper.ircan.org/ and the open-source code at https://github.com/IRCAN/EpitopeMapper.
(© The Author(s) 2026. Published by Oxford University Press.)
Competing Interests: G.K. is shareholder of Telomium, a company developing cancer vaccines. Other authors have no conflict of interest.
References: Nature. 2020 Sep;585(7823):107-112. (PMID: 32728218)
J Immunol. 2023 Jun 1;210(11):1677-1686. (PMID: 37083696)
J Immunol. 2002 Jul 15;169(2):739-49. (PMID: 12097376)
Sci Transl Med. 2013 Aug 7;5(197):197ra103. (PMID: 23926201)
J Immunol. 2025 Sep 1;214(9):2425-2433. (PMID: 40445715)
JCI Insight. 2019 Jun 20;5:. (PMID: 31219806)
Cell Rep. 2023 Aug 29;42(8):112827. (PMID: 37471227)
Acta Naturae. 2019 Oct-Dec;11(4):4-12. (PMID: 31993230)
Bioinformatics. 2017 Jan 1;33(1):104-111. (PMID: 27614350)
J Immunol. 2012 Jan 1;188(1):111-21. (PMID: 22140254)
BMC Bioinformatics. 2023 Dec 18;24(1):485. (PMID: 38110863)
Oncoimmunology. 2025 Dec;14(1):2460276. (PMID: 39891409)
J Immunother. 2013 Feb;36(2):133-51. (PMID: 23377668)
J Immunol. 2008 Mar 1;180(5):3122-31. (PMID: 18292535)
PLoS One. 2012;7(5):e36634. (PMID: 22615786)
Mol Cell Proteomics. 2007 Jan;6(1):102-13. (PMID: 17074750)
J Clin Invest. 2024 Mar 1;134(5):. (PMID: 38426497)
Sci Rep. 2016 Jul 11;6:29419. (PMID: 27406624)
Clin Cancer Res. 2009 Sep 1;15(17):5323-37. (PMID: 19723653)
Cell Genom. 2025 Aug 13;5(8):100946. (PMID: 40628266)
J Immunother Cancer. 2025 Jul 11;13(7):. (PMID: 40645662)
J Clin Invest. 2021 Feb 1;131(3):. (PMID: 33320837)
Substance Nomenclature: 0 (Autoantigens)
0 (Epitopes)
0 (Antigens, Neoplasm)
Entry Date(s): Date Created: 20260624 Date Completed: 20260624 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC13284612
DOI: 10.1093/nargab/lqag060
PMID: 42338745
Βάση Δεδομένων: MEDLINE
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  Data: Comprehensive mapping of identical sequences across human proteins emphasizes the widespread issue of shared epitopes in self-antigens.
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  Data: <searchLink fieldCode="AU" term="%22Kellermann+G%22">Kellermann G</searchLink>; Telomium SAS, Ivry-sur-Seine 94200, France.<br /><searchLink fieldCode="AU" term="%22Croce+O%22">Croce O</searchLink>; Université Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut Hospitalo-Universitaire (IHU) RespirERA, Fédération Hospitalo-Universitaire (FHU) OncoAge, Nice, France.<br /><searchLink fieldCode="AU" term="%22Mograbi+B%22">Mograbi B</searchLink>; Université Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut Hospitalo-Universitaire (IHU) RespirERA, Fédération Hospitalo-Universitaire (FHU) OncoAge, Nice, France.<br /><searchLink fieldCode="AU" term="%22Hofman+P%22">Hofman P</searchLink>; Université Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut Hospitalo-Universitaire (IHU) RespirERA, Fédération Hospitalo-Universitaire (FHU) OncoAge, Nice, France.; Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire (CHU) de Nice, IHU RespirERA, FHU OncoAge, Biobank BB-0033-00025, Nice, France.<br /><searchLink fieldCode="AU" term="%22Brest+P%22">Brest P</searchLink>; Université Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut Hospitalo-Universitaire (IHU) RespirERA, Fédération Hospitalo-Universitaire (FHU) OncoAge, Nice, France.
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  Data: Shared epitopes pose safety and efficacy issues for T-cell immunotherapy. To characterize the extent of this problem, we performed a computational analysis establishing a complete atlas of shared identical sequences across the human and murine proteomes. Unlike bacterial or viral antigens, self-antigens, including tumor-associated antigens (TAAs), frequently contain sequences of sufficient length to generate identical epitopes in other self-proteins. Epitopes from these shared sequences can theoretically reduce target specificity, confound immunomonitoring studies, and contribute to pre-existing immune tolerance toward TAAs. Notably, a subset of TAAs identified in this atlas is free of this drawback, providing a new criterion for antigen prioritization in cancer immunotherapy. To facilitate the detection of shared sequences, a web server has been made available at https://epitopemapper.ircan.org/ and the open-source code at https://github.com/IRCAN/EpitopeMapper.<br /> (© The Author(s) 2026. Published by Oxford University Press.)
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  Data: G.K. is shareholder of Telomium, a company developing cancer vaccines. Other authors have no conflict of interest.
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  Data: Nature. 2020 Sep;585(7823):107-112. (PMID: <searchLink fieldCode="PM" term="%2232728218%22">32728218)</searchLink><br />J Immunol. 2023 Jun 1;210(11):1677-1686. (PMID: <searchLink fieldCode="PM" term="%2237083696%22">37083696)</searchLink><br />J Immunol. 2002 Jul 15;169(2):739-49. (PMID: <searchLink fieldCode="PM" term="%2212097376%22">12097376)</searchLink><br />Sci Transl Med. 2013 Aug 7;5(197):197ra103. (PMID: <searchLink fieldCode="PM" term="%2223926201%22">23926201)</searchLink><br />J Immunol. 2025 Sep 1;214(9):2425-2433. (PMID: <searchLink fieldCode="PM" term="%2240445715%22">40445715)</searchLink><br />JCI Insight. 2019 Jun 20;5:. (PMID: <searchLink fieldCode="PM" term="%2231219806%22">31219806)</searchLink><br />Cell Rep. 2023 Aug 29;42(8):112827. (PMID: <searchLink fieldCode="PM" term="%2237471227%22">37471227)</searchLink><br />Acta Naturae. 2019 Oct-Dec;11(4):4-12. (PMID: <searchLink fieldCode="PM" term="%2231993230%22">31993230)</searchLink><br />Bioinformatics. 2017 Jan 1;33(1):104-111. (PMID: <searchLink fieldCode="PM" term="%2227614350%22">27614350)</searchLink><br />J Immunol. 2012 Jan 1;188(1):111-21. (PMID: <searchLink fieldCode="PM" term="%2222140254%22">22140254)</searchLink><br />BMC Bioinformatics. 2023 Dec 18;24(1):485. (PMID: <searchLink fieldCode="PM" term="%2238110863%22">38110863)</searchLink><br />Oncoimmunology. 2025 Dec;14(1):2460276. (PMID: <searchLink fieldCode="PM" term="%2239891409%22">39891409)</searchLink><br />J Immunother. 2013 Feb;36(2):133-51. (PMID: <searchLink fieldCode="PM" term="%2223377668%22">23377668)</searchLink><br />J Immunol. 2008 Mar 1;180(5):3122-31. (PMID: <searchLink fieldCode="PM" term="%2218292535%22">18292535)</searchLink><br />PLoS One. 2012;7(5):e36634. (PMID: <searchLink fieldCode="PM" term="%2222615786%22">22615786)</searchLink><br />Mol Cell Proteomics. 2007 Jan;6(1):102-13. (PMID: <searchLink fieldCode="PM" term="%2217074750%22">17074750)</searchLink><br />J Clin Invest. 2024 Mar 1;134(5):. (PMID: <searchLink fieldCode="PM" term="%2238426497%22">38426497)</searchLink><br />Sci Rep. 2016 Jul 11;6:29419. (PMID: <searchLink fieldCode="PM" term="%2227406624%22">27406624)</searchLink><br />Clin Cancer Res. 2009 Sep 1;15(17):5323-37. (PMID: <searchLink fieldCode="PM" term="%2219723653%22">19723653)</searchLink><br />Cell Genom. 2025 Aug 13;5(8):100946. (PMID: <searchLink fieldCode="PM" term="%2240628266%22">40628266)</searchLink><br />J Immunother Cancer. 2025 Jul 11;13(7):. (PMID: <searchLink fieldCode="PM" term="%2240645662%22">40645662)</searchLink><br />J Clin Invest. 2021 Feb 1;131(3):. (PMID: <searchLink fieldCode="PM" term="%2233320837%22">33320837)</searchLink>
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