The contractor will perform Key experimental approaches which include isolation of MHC-bound peptides from targeted tissues by mass-spectrometry, paired TCRa/TCRb receptor single-cell sequencing, large-scale functional screening of TCR libraries, multiplexed omics and FACS studies of T cell function, and computational prediction of T cell cross-reactivity. Epitopes recognized by effector, memory and regulatory T cells will be characterized, including those derived from self-proteins, endogenous retroviruses, and posttranslationally modified antigens. Diseases investigated include a spectrum from full-fledged autoimmunity, to environmentally-induced pathogenic T cell autoreactivity, to cases where T cell activation has been observed in the affected organ but the role in pathogenesis remains to be resolved.