TCRbeta CDR3 sequence of islet-infiltrating memory CD4 T cells in NOD mice. Mus musculus strain:NOD/ShiLtJ

Autoreactive memory CD4+ T cells play a critical role in the development of type 1 diabetes, but it is not yet known how the clonotypic composition and TCRβ repertoire of the memory CD4+ T cell compartment changes during the transition from prediabetes to diabetes. In this study, we used high-throughput sequencing to analyze the clonotypic composition and CDRβ diversity of sorted islet-infiltrating memory CD4+CD44high T cells from individual prediabetic and diabetic NOD mice. We found that the repertoire in both groups of mice is highly restricted to TRBV1 (Vβ2), TRBV13-3 (Vβ8.1), and TRBV19 (Vβ6) gene usage. This finding provides a strong rationale for targeting a limited number of TCR elements as a therapeutic approach to preventing and treating autoimmune diabetes.