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Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.The fundamental process of adaptive immunity relies on the differentiation of self from nonself. Nucleated cells are continuously monitored by effector cells of the immune system, which police the peptide status presented via cell surface molecules. Recent integrative structural approaches have provided insights toward our understanding of how sophisticated cellular machineries shape such hierarchical immune surveillance. Biophysical and structural achiev