Immunodominant T cell responses are important for virus clearance. However, the identification of immunodominant T cell peptide+HLA glycoprotein epitopes has been hindered by the extent of HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for new, immunodominant CD8+ T cell epitopes. The analysis targeted healthy HLA-A2+ and HLA-A2- donors. While M158A2 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three out of eight while, for the other five, prominent CD8+ T cell responses tended to focus on various peptides from the influenza nucleoprotein (NP) that were not presented by HLA-A2. In all the tested 7 A2- individuals, immunodominant responses all focused on NP. Importantly, most novel, immunodominant T cell epitopes identified by our study would not have been predicted by the current prediction programs as they are either too long or lacking typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8+ T cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.
- Copyright © 2013 by The American Association of Immunologists, Inc.