The importance of vaccines has renewed attention in part due to the global pandemic of SARS-CoV-2. Vaccine-induced effective factors that eliminate pathogens are antibodies and T cells. While antibodies recognize pathogen itself, T cells recognize antigen-MHC complexes presented by virus-infected cells. Therefore, in vaccine design, in addition to being able to induce functional and neutralizing antibodies, it is also important to have T cell epitopes that can induce superior T cells, including T cells which are cytotoxic [1], [2]. Cytotoxic T cells eliminate virus-infected cells and cancer cells, and this critical function is dependent on the intracellular antigen processing mechanisms that create antigen epitopes and assemble them into MHC complexes.

Indeed, the ideal vaccine design incorporates knowledge not only about T cell peptide epitopes, but also about the antigen processing pathway that generates these epitopes from their protein precursors and escorts them to be loaded onto MHC I molecules. However, to design effective vaccines, it is also important to understand antigen processing, where intracellular protein antigens are degraded and lead to the antigen presentation via MHC molecules [3]. In the current protein research, attention has focused on the so-called “birth to growth” steps of proteins, such as translation and modification, but degradation, the “death of proteins,” is also biologically important, and one of these steps is antigen processing.

In this paper, I would like to introduce the “KOVAK” system, a system for detecting antigen intermediates generated during antigen processing by utilizing biochemical methods originally designed by Professor Nilabh Shastri, and the role of molecular chaperones in antigen processing as discovered by utilizing this system.