||Makoto Yawata, Nobuyo Yawata, NK cell KIR heterogeneity and evolution, Elsevier Ltd, 10.1016/B978-0-12-370454-2.00006-5, 79-94, 2010.12, Human natural killer (NK) cells in the peripheral blood are highly diverse in their expression of HLA class I-specific inhibitory receptors. NK cell heterogeneity is generated by variegated expression of polymorphic MHC class I specific-inhibitory receptors. In humans, these receptors comprise the polygenic and polymorphic Killer cell Immunoglobulin-like Receptors (KIR), the more conserved NKG2A/CD94 receptors and the LILRB1 receptor. Variegated expression of these receptors generates a NK-cell repertoire that is unique to each human individual. The mechanism that shapes human NK cell repertoires is distinct from the selection mechanisms operating on T-lymphocyte and B-lymphocyte repertoires. Polygenic and polymorphic KIR combine with diverse HLA class I to determine KIR expression frequencies in the NK cell population, levels of cell-surface expression and the strength of missing-self response for each NK cell subset. Human NK cell expression of KIR and NKG2A is balanced to calibrate the overall response of repertoires against missing-self stimulus. Functional heterogeneity of NK cells is a feature of innate immunity that has been actively maintained in mammalian species through genetic diversification of NK receptors and their ligands. Understanding NK cell heterogeneity will become crucial in clinical medicine as NK cells are increasingly used in immunotherapy..