The Effect Cognate Antigen Has on T Cells Responding to Influenza Infection
Authors
Jones, Michael C.Faculty Advisor
Susan L. SwainAcademic Program
Immunology and MicrobiologyUMass Chan Affiliations
PathologyDocument Type
Doctoral DissertationPublication Date
2022-06-03Keywords
InfluenzaCD4 T cell
CD4 effector
CD4 memory
T cell memory
transition to memory
IL-2
trans presentation
survival
vaccine
protection.
Immunity
Immunology and Infectious Disease
Immunology of Infectious Disease
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The contributions of peptide antigen affinity for TCR in driving T cell memory is unclear. Effector CD4 T cells must recognize cognate antigen again at an effector checkpoint, 5-8 days post-infection, to generate an optimal memory population. In this thesis, we examined whether peptide affinity for the TCR of effectors impacts the extent of memory and degree of protection against rechallenge. We used an influenza A virus (IAV) nucleoprotein (NP)-specific TCR transgenic strain, FluNP, and generated NP- peptide variants that bind FluNP TCR with a broad range of avidity. Varying peptide avidity in vivo at the effector checkpoint revealed that higher affinity interactions yielded greater numbers of FluNP memory cells in the spleen and most dramatically in the lung and dLN. The major impact of avidity was on memory cell number, not cytokine production, and was already apparent within several days of transfer. These memory cells demonstrated enhanced protection against lethal IAV infection with a robust early day 5 secondary effector response in the lung. We previously showed that autocrine IL-2 production during the effector checkpoint prevented default effector apoptosis and supported memory formation. Here, peptide avidity determined the level of IL-2 produced by effectors while IL-2R expression was unaffected. However, IL-2Ra expression by APC drove more memory cell formation, suggesting that transpresentation of IL-2 by APC at this checkpoint enhanced CD4 memory generation. Secondary memory generation was also avidity-dependent. We propose this pathway selects CD4 effectors of highest affinity to progress to memory and can instruct future vaccine design.DOI
10.13028/2gnb-3h96Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32407Rights
Licensed under a Creative Commons licenseDistribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.13028/2gnb-3h96
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Except where otherwise noted, this item's license is described as Licensed under a Creative Commons license