Abstract
CD8+ cytotoxic T cells recognise and kill cancer cells that present immunogenic peptides bound to the cell surface major histocompatibility complex class I (MHC-I) molecules. The immunogenicity of these peptides derives from them being recognised as non-self after their parent proteins are intracellularly processed and presented as peptide-major histocompatibility complex class I (pMHC-I) complexes.
Highlights
CD8+ cytotoxic T cells recognise and kill cancer cells that present immunogenic peptides bound to the cell surface major histocompatibility complex class I (MHC-I) molecules
The immunogenicity of these peptides derives from them being recognised as non-self after their parent proteins are intracellularly processed and presented as peptide-major histocompatibility complex class I complexes. pMHC specific T cell receptor (TCR) recognition leads to cytotoxic T cell response
Lim has recently developed the EZ MHC-I assay using the peptide-major histocompatibility complex class I (pMHC-I) single chain trimer (SCT) molecule to enable a direct interrogation of the MHC ligandome predicted in silico or derived from patients’ samples
Summary
CD8+ cytotoxic T cells recognise and kill cancer cells that present immunogenic peptides bound to the cell surface major histocompatibility complex class I (MHC-I) molecules. Lim has recently developed the EZ MHC-I assay using the pMHC-I single chain trimer (SCT) molecule to enable a direct interrogation of the MHC ligandome predicted in silico or derived from patients’ samples. It is an assay based on empty MHC-I protein fragmentation to rapidly characterize bound peptides for affinity and stability [1]. This will exclude predicted binders which do not stabilize the MHC-I molecule, identify missed hits, and potentially enable neoantigen discovery with better characterized peptides. We describe the challenges of neoantigen selection, share missed hits identified by the EZ MHC-I assay, present the EZ MHC-I assay in greater details, and propose future SCT-based applications towards CD8+ T cell specific neoantigen discovery
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