A Theory of Immunodominance and Adaptive Regulation

Immunodominance refers to the phenomenon in which simultaneous T cell responses against multiple target epitopes organize themselves into distinct and reproducible hierarchies. In many cases, eliminating the response to the most dominant epitope allows responses to subdominant epitopes to expand more fully. The mechanism that drives immunodominance is still not well understood, although various hypotheses have been proposed. One of the more prevalent views is that immunodominance is driven by passive T cell competition for space on antigen presenting cells (APCs) or for access to specific MHC:epitope complexes on the surface of APCs. However, several experimental studies suggest that passive competition alone may not fully explain the robustness of immunodominance under physiological conditions or varying proportions of antigen-specific precursor T cells and APCs. These studies propose that a mechanism of active suppression among T cells gives rise to immunodominance.