A simple mathematical model helps to explain the immunodominance of CD8 T cells in influenza A virus infections

Understanding immunodominance, the phenomenon of epitope-specific T cells expanding in an often distinctly hierarchical fashion, is important for the design of T-cell-based intervention strategies. Several recent studies have investigated immunodominance of H-2Db-restricted CD8 T cells specific for the nucleoprotein NP366 and acid polymerase PA224 epitopes during influenza A virus infection of C57BL/6 mice. CD8 T cells specific for these two epitopes are codominant during primary infection; NP366 dominates during secondary infection. While a number of explanations for this observation have been proposed, none of them can fully account for all the observed data. In this article, we use a simple mathematical model to explain the seemingly inconsistent data. We show that the dynamic interactions between CD8 T cells and antigen presentation lead to a situation where CD8 T cells are limiting during the initial response whereas antigen is limiting in the secondary response. This “numbers game” between antigen and CD8 T cells can reproduce the observed immunodominance of the NP336- and PA224-specific CD8 T cells, thereby explaining the reported experimental data. Successful clearance of viral infections often relies on CD8 T cells (11, 23, 24). CD8 T cells (hereinafter also called cytotoxic T lymphocytes [CTL]) can recognize viral epitopes that are pre-sented by other cells on major histocompatibility complex (MHC