High-affinity tonic TCR:self-pMHC interactions inhibit T follicular helper cell development

Autor: Juliet M Bartleson, Ashley A Viehmann Milam, David L Donermeyer, Stephen Horvath, Paul M Allen
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Immunology. 204:230.7-230.7
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.204.supp.230.7
Popis: T cells receive tonic signals before encountering their immunogenic antigen, but whether or not peripheral, tonic TCR:self-pMHC interactions can affect a T cell’s response to foreign antigen remains relatively unexplored. We interrogated potential T effector functions controlled by tonic signaling with the use of a transgenic TCR system composed of two distinct CD4+ T cells that recognize the same Listerolysin O epitope but lie at opposite ends of the TCR:self-pMHC affinity spectrum. Remarkably, studies revealed differences in the ability of these two cells to produce Tfh cells during a primary immune response. The cells with lower-affinity tonic TCR:self-pMHC interactions generated a significantly greater frequency and total number of Tfh cells when compared to the high-affinity cells, which directly impacted the humoral immune response. To test whether affinity for self-pMHC controls Tfh development through tonic signaling, we generated two mouse lines: Scn5a/CD4-creERT2 and H2-DMf/f/UBC-creERT2. These mouse lines allow us to temporally increase or decrease tonic signaling, respectively. Results showed decreasing tonic self-pMHC availability did not allow for the survival of cells accustomed to high-affinity tonic TCR:self-pMHC interactions; however, increasing tonic signaling in cells that normally experience low-affinity TCR:self-pMHC interactions did indeed inhibit Tfh development. Furthermore, the H2-DMf/f mouse line was additionally crossed to various cre-strains to reveal that the CD11c+ antigen presenting cell subset is responsible for tonic signaling maintenance through presentation of self-pMHC. These studies reveal critical roles tonic signaling plays in Tfh development and CD4+ T cell survival.
Databáze: OpenAIRE
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