Harnessing the power of CD8+ T-cells: identification and validation of peptides bound to major histocompatibility complex class I by immunopeptidomics

In most successful vaccines, the protection is based on antibodies able to target a pathogen containing a stable antigen repertoire. However, vaccines for some hard to treat diseases such as HIV, malaria and tuberculosis, are not included in this group and require T cells for protection. T cell induced vaccines have been increasingly attractive to provide solutions to these important diseases as well as to tackle cancer and non-transmissible diseases, where non-self antigens are generated. CD8+ T cells are the effector cells able to identify and destroy virally infected or cancer cells, upon recognition of foreign antigens. For decades, the identity of non-self antigens has been pursued in an attempt to activate a long lasting CD8+ T cell response against the pathology of interest. Diverse strategies have been employed to harness the power of cytotoxic CD8+ T cells. Here we describe the biology of MHC class-I antigen processing and presentation, and discuss the most important strategies to study peptide-specific CD8+ T cells. Moreover, we focus on the most sophisticated and recent technology to identify peptide sequences presented by MHC class-I molecules to CD8+ T cells: immunopeptidomics.