High-throughput, targeted MHC class I immunopeptidomics using a functional genetics screening platform.

ABSTRACT: Identification of CD8⁺ T cell epitopes is critical for the development of immunotherapeutics. Existing methods for major histocompatibility complex class I (MHC class I) ligand discovery are time intensive, specialized and unable to interrogate specific proteins on a large scale. Here, we present EpiScan, which uses surface MHC class I levels as a readout for whether a genetically encoded peptide is an MHC class I ligand. Predetermined starting pools composed of >100,000 peptides can be designed using oligonucleotide synthesis, permitting large-scale MHC class I screening. We exploit this programmability of EpiScan to uncover an unappreciated role for cysteine that increases the number of predicted ligands by 9-21%, reveal affinity hierarchies by analysis of biased anchor peptid

SUBMITTER: Bruno PM 

PROVIDER: S-EPMC10314971 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature