Blood stage Plasmodium infection prevents recruitment of T follicular helper cells with high affinity T cell receptors 3412
Year: 2025
Type: article
Abstract: Description T follicular helper cells expand during immune challenge to provide T cell help for B cell responses, but it is unclear if there is a functional difference in Tfh with low or high-affinity TCRs in forming these responses. We used a micropipette assay to quantify the affinity of TCRs reactive to the lymphocytic choriomeningitis virus (LCMV) glycoprotein 66 (gp66) epitope on Tfh in three infection models: murine polyomavirus and Plasmodium yoelii, both engineered to express gp66, and LCMV. Our data demonstrate that, relative to native gp66 in LCMV infection and when expressed as a surrogate epitope on polyomavirus, P. yoeliigp66 infection expands Tfh with uniformly low affinity TCRs reactive to gp66. LCMV and polyomagp66 expanded Tfh harboring TCRs with a range of affinities. To extend our findings to an endogenous Plasmodium antigen, we quantified the affinity of TCRs on Tfh reactive to the PbTII endogenous epitope of Plasmodium heat shock protein 90. In results similar to those with gp66-reactive Tfh, we found that P. yoelii exclusively expands Tfh with low affinity PbTII specific TCRs. Again, this was Plasmodium specific as murine polyomaPbTII engineered to express the PbTII epitope expanded both high and low affinity PbTII-reactive TCRs. Collectively, this data shows that affinity of TCRs on Tfh is likely pathogen-driven as opposed to epitope-driven. This could have important implications for how Tfh affinity affects memory responses for vaccine design. Funding Sources Supported by NIH 5R01AI167422-03 Topic Categories Vaccines and Immunotherapy (VAC)
Source: The Journal of Immunology
Authors: Andelin G. Cardon, Jacob N. Kisiolek, Tracey J. Lamb, Brian D. Evavold
Institution: University of Utah
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Awards: G1545803332, In vitro, ex vivo, and in vivo evaluation of novel anti-SARS-CoV-2 nanobodies as safe and effective prophylactic and therapeutic options for Coronavirus Disease 2019, G4065380326, G43984215, Preparing for COVID-19 upcoming challenges by clinical and virological investigations, Engineering precision cancer immunotherapy, G6588985728, G738160294, Clinical study of flu-based and PD1-based vaccines for the SARS-CoV2, G9000294104
OpenAlex ID: W4416449737
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