Genetic Analysis of a Highly Homologous Gene Family: The Killer Cell Immunoglobulin-Like Receptors

Human natural killer (NK) cells express an array of inhibitory and activating receptors some of which interact with major histocompatibility complex (MHC) class I molecules. Expression of these receptors varies at a clonal level generating subsets of NK cells with respect to their receptor repertoire. These receptors can be divided into two broad groups: members of the C-type lectin family and those from the immunoglobulin superfamily (IgSF). The C-type lectins comprise the NKG2 family encoded by five genes (NKG2A, -C, -D, -E , and -F, NKG2B is an alternatively spliced transcript derived from NKG2A ) and CD94. CD94 can form a heterodimer with the NKG2A , B, C and E proteins and either NKG2A, -B , or -C with CD94 interact with the nonclassical class I molecule HLA-E (1 ). The NK cell receptors that are members of the IgSF are called the killer cell immunoglobulin-like receptors (KIRs), and a related set of loci is called the immunoglobulin-like transcripts (ILTs). Both the KIRs and the ILTs are encoded by tightly clustered groups of genes on human chromosome 19q13.4 in the leukocyte receptor complex (ref. 2 and 3 ). The KIRs are expressed on NK cells and a subset of T cells, whereas to date only one ILT, ILT-2, has been shown to be expressed on NK cells (4 ,5 ).