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Title: Regulation of T cell expansion by antigen presentation dynamics
An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response to infection while avoiding immunopathology. Recent experiments in mice have demonstrated that the expansion of a specific clone of T cells in response to cognate antigen obeys a striking inverse power law with respect to the initial number of T cells. Here, we show that such a relationship arises naturally from a model in which T cell expansion is limited by decaying levels of presented antigen. The same model also accounts for the observed dependence of T cell expansion on affinity for antigen and on the kinetics of antigen administration. Extending the model to address expansion of multiple T cell clones competing for antigen, we find that higher-affinity clones can suppress the proliferation of lower-affinity clones, thereby promoting the specificity of the response. Using the model to derive optimal vaccination protocols, we find that exponentially increasing antigen doses can achieve a nearly optimized response. We thus conclude that the dynamics of presented antigen is a key regulator of both the size and specificity of the adaptive immune response.  more » « less
Award ID(s):
1734030 1806501
PAR ID:
10099886
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
116
Issue:
13
ISSN:
0027-8424
Page Range / eLocation ID:
5914 to 5919
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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