How Reliable Are Predictions of CD8+ T Cell Epitope Recognition? Lessons for Cancer

Abstract

Synthetic peptides derived from antigen sequences are essential reagents for the detection of CD8+ cytotoxic T lymphocytes (CTLs), in assays such as ELISPOT/ImmunoSpot®. Indeed, the combination of peptides and ImmunoSpot® has been widely used for immune monitoring in numerous vaccine trials. Target antigens in pathogens or cancers may be large in size and multiple in number, often seemingly necessitating in silico peptide epitope predictions using algorithms and programs for certain HLA alleles to narrow down the numbers of required peptides. In this commentary, we discuss our data in the context of immune responses to viral and cancer antigens, concluding that systematic high-throughput immune monitoring of CD8+ T cells will provide more reliable insights on the host’s response to cancer than the reliance on select CD8+ T cell epitopes, no matter whether these are in silico predicted or even if they had been empirically established. We show the feasibility of large scale, high-throughput systematic CD8+ T cell epitope testing towards this goal.