Basic Principles in Modeling Adaptive Regulation and Immunodominance - Mathematical Methods and Models in Biomedicine - page 31

Basic Principles in Modeling Adaptive
Regulation and Immunodominance

Peter S. Kim, Peter P. Lee, and Doron Levy

1 Introduction

In this chapter we overview our recent work on mathematical models for the regula-
tion of the primary immune response to viral infections and immunodominance. The
primary immune response to a viral infection can be very rapid, yet transient. Prior
to such a response, potentially reactive T cells wait in lymph nodes until stimulated.
Upon stimulation, these cells proliferate for a limited duration and then undergo
apoptosis or enter dormancy as memory cells. The mechanisms that trigger the
contraction of the T cell population are not well understood. 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. Likewise, if the two most dominant
epitopes are removed, then the third most dominant response may expand. The
mechanisms that drive immunodominance are also not well understood.
In order to understand the processes that control the T cells expansion and
contraction, Mercado et al. demonstrated experimentally that the kinetics of CD8

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T cell expansion and contraction are determined within the first day of infection

P. S . K i m ( )
School of Mathematics and Statistics, University of Sydney, NSW 2006, Australia
e-mail: [e-mail]
P. P. L e e
Division of Hematology, Department of Medicine, Stanford University, Stanford, CA 94305,
USA
e-mail: [e-mail]
D. Levy
Department of Mathematics and Center for Scientific Computation and Mathematical Modeling
(CSCAMM), University of Maryland, College Park, MD 20742, USA
e-mail: [e-mail]