KIR3DL1

KIR3DL1 is a gene encoding a killer cell immunoglobulin-like receptor (KIR) found in humans. KIR3DL1 belongs to the KIR family of receptors expressed on natural killer (NK) cells and some T cells. These receptors regulate the cytotoxic activity of NK cells by interacting with major histocompatibility complex (MHC) class I molecules on target cells.

Function:

The KIR3DL1 protein is an inhibitory receptor, meaning that upon engagement with its cognate MHC class I ligand, it transmits a negative signal that inhibits NK cell activation. This inhibition prevents NK cells from killing healthy cells that express the appropriate MHC class I molecule. KIR3DL1 recognizes specific HLA-B allotypes, with its best-defined ligand being HLA-Bw4. The specificity of the interaction between KIR3DL1 and its HLA-B ligand is genetically determined and varies among individuals.

Genetics:

The KIR3DL1 gene is located within the leukocyte receptor complex (LRC) on chromosome 19q13.4. The KIR locus is highly polymorphic, with significant variation in the number and type of KIR genes present in different individuals. This genetic diversity contributes to differences in NK cell function and susceptibility to diseases. KIR3DL1 itself also exists in allelic variants, some of which are associated with differences in receptor expression levels and ligand binding affinity. A variant lacking a portion of exon 5 results in a soluble form of KIR3DL1 (sKIR3DL1).

Clinical Significance:

Variations in KIR3DL1 and its interactions with HLA-B have been implicated in a variety of diseases, including viral infections (such as HIV), autoimmune diseases, and cancer. For example, certain KIR3DL1 alleles, in combination with specific HLA-B alleles, have been associated with slower progression to AIDS in HIV-infected individuals. Furthermore, KIR3DL1 and its ligands are involved in the regulation of alloreactivity in hematopoietic stem cell transplantation. The presence or absence of specific KIR/HLA combinations can influence the outcome of transplantation by modulating NK cell-mediated graft-versus-leukemia effects and graft-versus-host disease.