Research ArticleHUMAN IMMUNOLOGY

Class I HLA haplotypes form two schools that educate NK cells in different ways

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Science Immunology  09 Sep 2016:
Vol. 1, Issue 3, pp. eaag1672
DOI: 10.1126/sciimmunol.aag1672

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NK cell immunity gets schooled

Population-level genetic analysis can give us clues as to which factors guide immune evolution. Now, Horowitz et al. have applied this analysis to polymorphisms in HLA that affect NK cell education. They find that the HLA-B haplotype −21M that delivers functional peptides to the conserved CD94/NKG2A receptor rarely encodes ligands for the more diverse killer cell immunoglobulin-like receptors (KIRs), in contrast to the haplotype −21T, which does not deliver functional peptides. Individuals homo- or heterozygous for −21M are more likely to have more diverse CD94/NKG2A+ NK cells, suggesting that these HLA haplotypes may have specialized to either the KIR or CD94/NKG2A school through complementary coevolution.