Basic Principles in Modeling Adaptive Regulation and Immunodominance - Mathematical Methods and Models in Biomedicine - page 53

One of the consequences of our work is that immunodominance provides a means
of peripheral positive selection that may be optimal in most circumstances, since it
generates highly adapted responses against specifically targeted antigens (a response
that targets the most reactive clones). Such a pattern must be disadvantageous
against rapidly evolving pathogens such as HIV or cancer that can evade narrow
T cell responses. Hence, our model of iTreg-mediated immunodominance may have
implications for improving therapy via T cell vaccinations. In particular, our model
suggests a possible negative correlation between immunodominance, driven by
contraction, and epitope spread, driven by expansion. In this case, the strength and
timing of the iTreg response may cause a shift in T cell dynamics toward a narrower
or broader response, i.e., toward immunodominance or epitope spread. From these
results, we hypothesize that temporarily suppressing the de novo generation of
iTregs following T cell vaccination may result in a broader T cell response than
normal against multiple target epitopes, which will then make it more likely for the
immune system to eliminate rapidly evolving targets that would otherwise escape
immune detection.

Acknowledgements This work was supported in part by the joint NSF/NIGMS program under
Grant Number DMS-0758374 and in part by Grant Number R01CA130 817 from the National
Cancer Institute. The content is solely the responsibility of the authors and does not necessarily
represent the official views of the National Cancer Institute or the National Institutes of Health.

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