Loading...
Thumbnail Image
Publication

The Effect Cognate Antigen Has on T Cells Responding to Influenza Infection

Jones, Michael C.
Citations
Altmetric:
Student Authors
Faculty Advisor
Academic Program
Immunology and Microbiology
UMass Chan Affiliations
Document Type
Doctoral Dissertation
Publication Date
2022-06-03
Subject Area
Embargo Expiration Date
Link to Full Text
Abstract

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.

Source
Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.13028/2gnb-3h96
PubMed ID
Other Identifiers
Notes
Funding and Acknowledgements
Corresponding Author
Related Resources
Related Resources
Repository Citation
Rights
Licensed under a Creative Commons license