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- W4313405739 abstract "Abstract Regulatory T cells (Tregs) are critical in preventing autoimmunity and express a unique TCR repertoire with high affinity to self-antigens. However, whether Treg and effector T cell (Teff) TCR repertoires are similarly divergent in the context of autoimmunity, and whether Tregs are able to maintain TCR affinity advantage has not been clearly defined. Insulin tetramer positive Tregs isolated from pancreatic islets of NOD mice showed a higher level of self-reactivity (CD5) and TCR signaling (Nur77-GFP) than Teffs specific to the same epitope. We isolated and sequenced insulin tetramer+ Teffs and Tregs from islets of NOD mice expressing a fixed TCRα of an insulin specific TCR. Surprisingly, significant overlap was identified between Treg and Teff TCR repertoires, suggesting that similar TCRs can support autoimmune Treg and Teff development and recruitment into the autoimmune response. Both Tregs and Teffs exhibited TCRs with a broad range of reactivity to insulin epitope and Treg TCRs did not show increased reactivity. The disconnect between Nur77-GFP and TCR functional affinity suggests a Treg cell-intrinsic capacity to compete for antigen or to enhance downstream signaling. When re-expressed in vivo using the TCR retrogenic method, Treg derived TCRs showed lower Treg generation and collectively higher diabetogenicity. With comparable Treg generation, low affinity Treg TCR showed significantly lower protection against diabetes than high affinity Treg TCR. These findings indicate that in tissue specific autoimmunity Tregs can express a TCR repertoire with a broad range of functionality and have significant overlap with Teffs of the same specificity, which might negatively affect their suppressive capacity. This work was supported by the NIH (AI125301-01A1) and The Robert and Janice McNair Foundation." @default.
- W4313405739 created "2023-01-06" @default.
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- W4313405739 date "2022-05-01" @default.
- W4313405739 modified "2023-09-25" @default.
- W4313405739 title "Insulin specific TCR repertoire analysis reveals functional diversity of Treg TCRs" @default.
- W4313405739 doi "https://doi.org/10.4049/jimmunol.208.supp.104.04" @default.
- W4313405739 hasPublicationYear "2022" @default.
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