Structural dissimilarity from self drives neoepitope escape from immune tolerance.

Details

Serval ID
serval:BIB_186F0AD1C570
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Structural dissimilarity from self drives neoepitope escape from immune tolerance.
Journal
Nature chemical biology
Author(s)
Devlin J.R., Alonso J.A., Ayres C.M., Keller GLJ, Bobisse S., Vander Kooi C.W., Coukos G., Gfeller D., Harari A., Baker B.M.
ISSN
1552-4469 (Electronic)
ISSN-L
1552-4450
Publication state
Published
Issued date
11/2020
Peer-reviewed
Oui
Volume
16
Number
11
Pages
1269-1276
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
T-cell recognition of peptides incorporating nonsynonymous mutations, or neoepitopes, is a cornerstone of tumor immunity and forms the basis of new immunotherapy approaches including personalized cancer vaccines. Yet as they are derived from self-peptides, the means through which immunogenic neoepitopes overcome immune self-tolerance are often unclear. Here we show that a point mutation in a non-major histocompatibility complex anchor position induces structural and dynamic changes in an immunologically active ovarian cancer neoepitope. The changes pre-organize the peptide into a conformation optimal for recognition by a neoepitope-specific T-cell receptor, allowing the receptor to bind the neoepitope with high affinity and deliver potent T-cell signals. Our results emphasize the importance of structural and physical changes relative to self in neoepitope immunogenicity. Considered broadly, these findings can help explain some of the difficulties in identifying immunogenic neoepitopes from sequence alone and provide guidance for developing novel, neoepitope-based personalized therapies.
Pubmed
Web of science
Create date
15/09/2020 10:22
Last modification date
23/11/2020 6:24
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