The KIR gene family: life in the fast lane of evolution

Abstract

A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). An interesting facet of the KIR family is the unusual variability of the respective gene cluster, which is changing shape at an astonishing evolutionary pace. Not only do KIR genes come in different allelic variants, but the KIR locus has also gone through drastic contractions and expansions in recent evolutionary history, resulting in a wide variety of KIR haplotypes. A new study now reveals how an originally nonfunctional KIR pseudogene, KIR3DP1, is brought back to life in certain individuals via non-reciprocal recombination between two different KIR haplotypes. This Commentary outlines how the unique architecture of the KIR locus facilitates the generation of new KIR haplotypes and discusses the functional relevance of it.