Prediction of neo-epitope immunogenicity reveals TCR recognition determinants and provides insight into immunoediting.

Details

Serval ID
serval:BIB_9AA90BD897A9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prediction of neo-epitope immunogenicity reveals TCR recognition determinants and provides insight into immunoediting.
Journal
Cell reports. Medicine
Author(s)
Schmidt J., Smith A.R., Magnin M., Racle J., Devlin J.R., Bobisse S., Cesbron J., Bonnet V., Carmona S.J., Huber F., Ciriello G., Speiser D.E., Bassani-Sternberg M., Coukos G., Baker B.M., Harari A., Gfeller D.
ISSN
2666-3791 (Electronic)
ISSN-L
2666-3791
Publication state
Published
Issued date
16/02/2021
Peer-reviewed
Oui
Volume
2
Number
2
Pages
100194
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
CD8+ T cell recognition of peptide epitopes plays a central role in immune responses against pathogens and tumors. However, the rules that govern which peptides are truly recognized by existing T cell receptors (TCRs) remain poorly understood, precluding accurate predictions of neo-epitopes for cancer immunotherapy. Here, we capitalize on recent (neo-)epitope data to train a predictor of immunogenic epitopes (PRIME), which captures molecular properties of both antigen presentation and TCR recognition. PRIME not only improves prioritization of neo-epitopes but also correlates with T cell potency and unravels biophysical determinants of TCR recognition that we experimentally validate. Analysis of cancer genomics data reveals that recurrent mutations tend to be less frequent in patients where they are predicted to be immunogenic, providing further evidence for immunoediting in human cancer. PRIME will facilitate identification of pathogen epitopes in infectious diseases and neo-epitopes in cancer immunotherapy.
Keywords
TCR recognition, immunoediting, immunogenicity, neo-epitope predictions, tumor immunology
Pubmed
Open Access
Yes
Create date
16/03/2021 10:29
Last modification date
07/04/2021 6:34
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