Reversion analysis reveals the in vivo immunogenicity of a poorly MHC I-binding cancer neoepitope.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_63F82E17F0C1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Reversion analysis reveals the in vivo immunogenicity of a poorly MHC I-binding cancer neoepitope.
Journal
Nature communications
Author(s)
Ebrahimi-Nik H., Moussa M., Englander R.P., Singhaviranon S., Michaux J., Pak H., Miyadera H., Corwin W.L., Keller GLJ, Hagymasi A.T., Shcheglova T.V., Coukos G., Baker B.M., Mandoiu I.I., Bassani-Sternberg M., Srivastava P.K.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
05/11/2021
Peer-reviewed
Oui
Volume
12
Number
1
Pages
6423
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
High-affinity MHC I-peptide interactions are considered essential for immunogenicity. However, some neo-epitopes with low affinity for MHC I have been reported to elicit CD8 T cell dependent tumor rejection in immunization-challenge studies. Here we show in a mouse model that a neo-epitope that poorly binds to MHC I is able to enhance the immunogenicity of a tumor in the absence of immunization. Fibrosarcoma cells with a naturally occurring mutation are edited to their wild type counterpart; the mutation is then re-introduced in order to obtain a cell line that is genetically identical to the wild type except for the neo-epitope-encoding mutation. Upon transplantation into syngeneic mice, all three cell lines form tumors that are infiltrated with activated T cells. However, lymphocytes from the two tumors that harbor the mutation show significantly stronger transcriptional signatures of cytotoxicity and TCR engagement, and induce greater breadth of TCR reactivity than those of the wild type tumors. Structural modeling of the neo-epitope peptide/MHC I pairs suggests increased hydrophobicity of the neo-epitope surface, consistent with higher TCR reactivity. These results confirm the in vivo immunogenicity of low affinity or 'non-binding' epitopes that do not follow the canonical concept of MHC I-peptide recognition.
Pubmed
Web of science
Open Access
Yes
Create date
16/11/2021 9:09
Last modification date
12/01/2022 7:10
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