GSE139544 A critical insulin TCR contact residue selects high affinity and pathogenic insulin specific T cells

Contributors : Matthew Bettini ; Maria Bettini ; Marissa Scavuzzo ; Malgorzata BorowiakSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusType 1 Diabetes (T1D) is an autoimmune mediated disease that culminates in the targeted destruction of insulin producing β cells. CD4 responses in non-obese diabetic mice are dominated by InsB9-23 specificity, and mutation of the key TCR contact residue within the epitope prevents diabetes development. However, it is not clear how insulin self-antigen controls the selection of autoimmune and T regulatory cells. Here we demonstrate that mutation of insulin epitope results in escape of highly pathogenic T cells. We observe an increase in antigen reactivity, clonality and pathogenicity of insulin specific T cells that develop in the absence of cognate antigen. Using single TCR system, we demonstrate that Treg de velopment is greatly diminished in mice with Y16A mutant epitope. Collectively, these results suggest that the tyrosine residue at position 16 is necessary to constrain TCR reactivity for InsB9-23 by both limiting the development of pathogenic T cells and supporting the selection of regulatory T cel ls.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research