The genetic basis of autoimmunity seen through the lens of T cell functional traits

Autoimmune disease heritability is enriched in T cell-specific regulatory regions of the genome. Modern-day T cell datasets now enable association studies between single nucleotide polymorphisms (SNPs) and a myriad of molecular phenotypes, including chromatin accessibility, gene expression, transcriptional programs, T cell antigen receptor (TCR) amino acid usage, and cell state abundances. Such studies have identified hundreds of quantitative trait loci (QTLs) in T cells that colocalize with genetic risk for autoimmune disease. The key challenge facing immunologists today lies in synthesizing these results toward a unified understanding of the autoimmune T cell: which genes, cell states, and antigens drive tissue destruction?