{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:34:03Z","timestamp":1781822043583,"version":"3.54.5"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":59,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Inova-FIOCRUZ"},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Antigen recognition by CD8+ T-cell receptors (TCR) is crucial for immune responses to pathogens and tumors. TCRs are cross-reactive, a single TCR can recognize multiple peptide-Human Leukocyte Antigen (HLA) complexes. The study of cross-reactivity can support the development of therapies focusing on immune modulation, such as the expansion of pre-existing T-cell clones to fight pathogens and tumors. The peptide-HLA (pHLA) surface has previously been used to identify TCR cross-reactivities. In the present work, we sought to perform a comprehensive analysis of peptide-HLA by selecting thousands of human and viral epitopes. We profit from established docking models to identify features from different spatial perspectives of HLA-A*02:01, explore similarities between self and non-self epitopes, and list potential cross-reactive epitopes of therapeutic interest. A total of 2631 unique epitopes from representative viral proteins or human proteins were modeled. We were able to demonstrate that cross-reactive CDR3 sequences from public databases recognize epitopes with similar electrostatic potential, charge, and spatial location. Using data from published studies that measured T-cell reactivity to mutated epitopes, we observed a negative correlation between epitope dissimilarity and T-cell activation. Most analysed cancer epitopes were more similar to self epitopes, yet we identified features distinguishing those more similar to viral antigens. Finally, we enumerated potential cross-reactivities between tumoral and viral epitopes and highlighted some challenges in their identification for therapeutic use. Moreover, the thousands of peptide-HLA complexes generated in our work constitute a valuable resource to study T-cell cross-reactivity.<\/jats:p>","DOI":"10.1093\/bib\/bbaf012","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T13:15:06Z","timestamp":1737378906000},"source":"Crossref","is-referenced-by-count":1,"title":["Unveiling cross-reactivity: implications for immune response modulation in cancer"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9511-294X","authenticated-orcid":false,"given":"Marco Ant\u00f4nio M","family":"Pretti","sequence":"first","affiliation":[{"name":"Laboratory of Bioinformatics and Computational Biology, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA) , Rio de Janeiro ,","place":["Brazil"]},{"name":"Program of Cell and Gene Therapy, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA) , Rio de 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