Abstract
A major question in immunology is what role antigen load plays in determining the size of the CD8 immune response. Is the amount of antigen important during recruitment, proliferation, and/or memory formation? Animal studies have shown that antigen is only strictly required early during activation of T cells, but the importance of antigen at later timepoints is unclear. Using data from 24 volunteers infected with the yellow fever vaccine virus (YFV), we analyzed the dependence of T cell proliferation upon viral load. We found that volunteers with high viral load initially have greater T cell responses, but by 28 days post-vaccination those with lower viral load are able to ‘catch-up.’ Using differential equation modeling we show that this pattern is consistent with viral load only affecting recruitment (i.e., programmed proliferation) as opposed to affecting recruitment and proliferation (i.e., antigen-dependent proliferation). A quantitative understanding of the dependence of T cell dynamics on antigen load will be of use to modelers studying not only vaccination, but also cancer immunology and autoimmune disorders.
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This work was supported by four NIH Grants NIH U54GM111274, NIH R01AI110720 (to R. Antia), NIH U19AI11789102 (to R. Antia and R. Ahmed), and U19AI057266 (to R. Ahmed).
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Moore, J.R., Ahmed, H., McGuire, D. et al. Dependence of CD8 T Cell Response upon Antigen Load During Primary Infection. Bull Math Biol 81, 2553–2568 (2019). https://doi.org/10.1007/s11538-019-00618-9
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DOI: https://doi.org/10.1007/s11538-019-00618-9