Identification of tissue-specific autoantigens in mice with a Treg specific deletion of Helios

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B741
Abstract ID: 5368

Presenting Author:
Angela M Thornton , Staff Scientist at NIAID, NIH

Abstract:

The selective deletion of the transcription factor Helios in Regulatory T Cells (cKO) results in systemic immune activation and hypergammaglobulinemia in C57BL/6 mice. While Foxp3 deficient mice develop autoimmune damage in multiple organs, cKO mice only manifest autoimmunity in adipose tissue. Analysis of adipose tissue revealed a significant lymphocytic infiltrate comprised predominantly of CD8⁺ T cells. The loss of adipocytes was dependent on CD8⁺ T cells as cKO mice crossed to ß-2 microglobulin deficient mice maintain normal adipose tissue. cKO mice also develop autoantibodies to adipocyte antigens as detected by western blots. To identify potential T cell target antigens, we first examined potential targets of autoantibodies using Phage Immunoprecipitation-Sequencing (PhIP-Seq) which uses a proteome-wide phage-display library to interrogate serum for autoantibodies. A prominent antigen target was PLIN1 (perilipin), an abundant adipocyte protein. We also crossed cKO mice to the BALB/c background. Surprisingly these mice also exhibit autoimmune lipodystrophy. PhIP-Seq on these mice also identified PLIN1 as a protein target. As antibody specificity may mirror T cell specificity, the identification of B cell epitopes provides a targeted approach to identify adipose-specific T cell epitopes. The identification of a T cell target autoantigen should facilitate the characterization of the autoantigen-specific T cell repertoire and the role of Treg in preventing autoimmunity.