Mathematical Biology Seminar

Paul Thomas
St. Jude's Children's Research Hospital
Wednesday Dec. 5, 2007
3:05pm in LCB 215
"CD8 T cell epitope recognition: broad detection through a narrow window"

Abstract: Immunodominance is a phenomenon where lines of CD8+ T cells that respond to particular epitope dominate the immune response. In influenza infections of mice, the immunodominance hierarchy to seven epitopes is well defined in both primary and secondary responses. Previous work led to the hypothesis that this hierarchy results from a combination of epitope density and precursor frequency. Using a new accurate method for measuring epitope density, we found a surprisingly broad dynamic range of epitope presentation, from 10^2 to 10^6 peptides/cell, varying by as much as three orders of magnitude over 24 hours. Immunodominant T cells lineages were associate with epitopes that started at high levels and then dropped, and secondary T cells lineages with those that started at low levels and increased. Fitting a differential equations model indicates that, for secondary responses, epitope densities detected at early time points (<6 hours) contribute most to immunodominance. The success of this model indicates that under situations of high competition between several epitopes, the primary determinants of immunodominance are early epitope densities and precursor frequency. When lower levels of competition are present, the model predicts the window of epitope detection lengthens, a finding consistent with data derived from ongoing studies in the lab and suggesting that the model may be predictive of in vivo responses.