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

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 fro

SUBMITTER: Ebrahimi-Nik H 

PROVIDER: S-EPMC8571378 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature