High-throughput sequencing of gluten-specific T cells in celiac disease

Abstract

Celiac disease is a chronic inflammatory disorder resulting from mis-appropriate immune response toward ingested glu-ten proteins. Gluten-specific CD4+ T cells, as the key drivers for the pathogenesis can be identified by staining with HLA-DQ:gluten tetramers. In this project, we conducted single cell transcriptome sequencing on CD4+ T cells sampled from peripheral blood of untreated CD patients. The tetramer-specific T cells showed transcriptomic profiles consistent with activated effector memory T cells that share features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in metabolic processes, including fatty acid metabolism and redox potentials. In addition, we utilized the unique expression of immune receptor of each T and B cell to quantify the impact of index switching on single cell RNA-seq experiments. We also demonstrated that the state of celiac disease could be inferred by unbiased direct TCR sequencing on lamina propria T cells, which is promising for the ultimate goal of inferring celiac disease state based on TCR sequencing of cir-culating T cells.