Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model.

ABSTRACT: Roughly one-half of mice with partial defects in two immune tolerance pathways (Aire^GW/+Lyn^-/- mice) spontaneously develop severe damage to their retinas due to T cell reactivity to Aire-regulated interphotoreceptor retinoid-binding protein (IRBP). Single-cell T cell receptor (TCR) sequencing of CD4⁺ T cells specific for a predominate epitope of IRBP showed a remarkable diversity of autoantigen-specific TCRs with greater clonal expansions in mice with disease. TCR transgenic mice made with an expanded IRBP-specific TCR (P2.U2) of intermediate affinity exhibited strong but incomplete negative selection of thymocytes. This negative selection was absent in IRBP^-/- mice and greatly defective in Aire^GW/+ mice. Most P2.U2^+/- mice

SUBMITTER: Yin M 

PROVIDER: S-EPMC10835137 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature