Regulation of T cell expansion by antigen presentation dynamics.

TitleRegulation of T cell expansion by antigen presentation dynamics.
Publication TypeJournal Article
Year of Publication2019
AuthorsMayer, A, Zhang, Y, Perelson, AS, Wingreen, NS
JournalProc Natl Acad Sci U S A
Date Published2019 03 26
KeywordsAnimals, Antigen Presentation, Immunity, Cellular, Lymphocyte Activation, Mice, Mice, Transgenic, Models, Immunological, Models, Theoretical, T-Lymphocytes, Vaccination

<p>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.</p>

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID30850527
PubMed Central IDPMC6442601
Grant ListR01 AI028433 / AI / NIAID NIH HHS / United States
R01 OD011095 / OD / NIH HHS / United States
R25 GM067110 / GM / NIGMS NIH HHS / United States