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Synthesis Increases Markedly over the Course of Infection and Correlates with Immunodominance1
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
Primary CD8+ T cell responses play a major role in controlling infection by many viruses, and CD8+ memory T cells can confer immunity to virus challenge. In this study we report that for many epitope-specific CD8+ T cell populations, the regulation of an important effector molecule, IFN-
, changes dramatically over the course of infection. During the acute phase of infection, many CD8+ T cells exhibit a significant lag before producing IFN- in response to Ag contact; in contrast, the onset of IFN- production by memory cells of the same epitope specificity is markedly accelerated. The biological consequences of this improved responsiveness are manifold. Moreover, during the acute phase of the CD8+ T cell response when immunodominance is being established, there is a strong correlation (p = 0.0002) between the abundance of each epitope-specific T cell population and the rapidity with which it initiates IFN- synthesis. Previous studies have indicated that IFN- plays a critical role in determining the immunodominance hierarchy of an on-going T cell response, and in this report we present evidence for an underlying mechanism: we propose that the CD8+ T cells that most rapidly initiate IFN- production may be at a selective advantage, permitting them to dominate the developing T cell response.
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