Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution

• Published in: Nature reviews. Immunology Vol. 13; no. 2; pp. 133 - 144
• Main Authors: Parham, Peter, Moffett, Ashley
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2013; Nature Publishing Group
• Subjects: 631/181; 631/250/21/324/1509; 631/443/494; Animals; Biological Evolution; Biomedical and Life Sciences; Biomedicine; Brain; Cell migration; Cell receptors; Continents; Evolution; Evolution, Molecular; Evolutionary genetics; Genetic aspects; Haplotypes; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Human evolution; Humans; Immunity; Immunity - genetics; Immunity - immunology; Immunology; Killer cells; Major histocompatibility complex; Migration; Natural killer cells; opinion-2; Pan troglodytes; Physiological aspects; Primates; Protein Binding; Protein Stability; Receptors, Natural Killer Cell - genetics; Receptors, Natural Killer Cell - immunology; Receptors, Natural Killer Cell - metabolism; Reproduction; Reproduction - genetics; Reproduction - immunology; United States; United Kingdom
• ISSN: 1474-1733; 1474-1741; 1474-1741
• DOI: 10.1038/nri3370

The role of natural killer (NK) cells in both immunity to infection and reproductive success is postulated to have placed competing demands on the evolution of NK cell receptors and their MHC class I ligands during the migration of humans out of Africa. Natural killer (NK) cells have roles in immunity and reproduction that are controlled by variable receptors that recognize MHC class I molecules. The variable NK cell receptors found in humans are specific to simian primates, in which they have progressively co-evolved with MHC class I molecules. The emergence of the MHC-C gene in hominids drove the evolution of a system of NK cell receptors for MHC-C molecules that is most elaborate in chimpanzees. By contrast, the human system of MHC-C receptors seems to have been subject to different selection pressures that have acted in competition on the immunological and reproductive functions of MHC class I molecules. We suggest that this compromise facilitated the development of the bigger brains that enabled archaic and modern humans to migrate out of Africa and populate other continents.