Dependence of CD8 T Cell Response upon Antigen Load During Primary Infection: Analysis of data from Yellow Fever vaccination

• Type of Material: Article
• Authors: James Moore, Fred Hutchinson Cancer Research Center; hasan Ahmed, Emory University; Don McGuire, Emory University; Rama Akondy, Emory University; Rafi Ahmed, Emory University; Rustom Antia, Emory University
• Language: English
• Date: 2019-06-04
• Publisher: Springer Nature
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019, Society for Mathematical Biology
• Final Published Version (URL): https://doi.org/10.1007/s11538-019-00618-9
• Title of Journal or Parent Work: Bulletin of Mathematical Biology
• Volume: 81
• Issue: 7
• Start Page: 2553
• End Page: 2568
• Grant/Funding Agency: NIH
• Grant/Funding Information: 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).
• Keywords: T cell Proliferation; Programmed Proliferation; Yellow Fever Vaccine
• Subject - Topics: Immunology

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.