Therapies focused on sustaining or promoting endogenous insulin production for individuals at risk for or with T1D will require a thorough understanding of the gene expression patterns in islet α, β, and δ cells from control subjects and from individuals with T1D. Toward that end, we have developed methods to essentially purify α, β, and δ cells from human pancreata by intracellular staining for specified intracellular hormone content, sorting the populations by flow cytometry, then obtaining detailed transcriptomes from each population using next generation RNA sequencing. We propose to define the transcriptomes of isolated α, β, and δ cells from those with and without T1D and from β cells with varying HLA Class I expression (dim or bright) from subjects with T1D. We will define the changes in genes expressed by islet cells under the pathological conditions of T1D and specifically, from β and α cells hyper-expressing Class I proteins as a potential marker o a pro-inflammatory microenvironment with islets. These studies elucidate the β and α cell dysfunction in T1D and may provide targets for future therapeutic intervention(s) in T1D.