Mining for Treasures: Systematic Profiling of 8-, 9-, 10-, and 11-mer HLA-B*0702-restricted CD8+ T cell epitopes from the Influenza A/Puerto Rico/8/34 (H1N1) Virus Hemagglutinin with Potential Application in Vaccine Development (B193)

Abstract

Abstract Identification of T cell epitopes is of crucial importance for the development of cancer and viral T cell eliciting vaccines. Here, we define CD8+ T cell epitopes using a novel high-throughput system for the synthesis and screening of peptide libraries that include all dominant epitope lengths (8–11mers) for MHC class I molecules. These representative peptide libraries are tested for their ability to bind various MHC class I molecules in a competitive manner. This comprehensive screening strategy begins with the synthesis of an overlapping truncated peptide library containing mixes of four peptides with a common C terminus, but having a length of 8, 9, 10, or 11 residues. Following the initial screen, positive hits are resolved into individual epitope responses. In order to identify HLA-B*0702-restricted epitopes, a peptide library was prepared for the influenza A virus Hemagglutinin (HA) protein. Screening results revealed 63 high/medium affinity epitopes at various sizes. A number of these putative influenza epitopes coincide with directly discovered influenza epitopes as well as influenza epitopes reportedly recognized by CTL. In conclusion, this study demonstrates that the rapid and methodical screening of T cell immune epitope libraries can help in detecting and monitoring infections as well as enabling immune intervention strategies with respect to treatment or prevention of the disease.