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

Authors

Guillaume Kellermann, Olivier Croce, Baharia Mograbi, Paul Hofman, Patrick Brest

Published in

NAR genomics and bioinformatics. Volume 8. Issue 2. Pages lqag060. Epub Jun 22, 2026.

Abstract

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.

PMID:
42338745
Bibliographic data and abstract were imported from PubMed on 24 Jun 2026.

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