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Cover of The KIR Gene Cluster

The KIR Gene Cluster

and .

Author Information

1 and 2.

1 Basic Research Program, SAIC, Inc., National Cancer Institute, Frederick, MD, USA. vog.frcficn.liam@tgnirrac
2 South Thames Clinical Transplantation Laboratory, Guys Hospital, London, UK. ude.drofnats@namron.luap

Excerpt

Killer cell immunoglobulin-like receptors (KIRs) are members of a group of regulatory molecules found on subsets of lymphoid cells. They were first identified by their ability to impart some specificity on natural killer (NK) cytolysis. The KIR locus, containing a family of polymorphic and highly homologous genes, maps to chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The LRC also encodes the leukocyte Ig-like receptor family (LILR), the leukocyte-associated inhibitory receptor (LAIR) family, and the Fcα receptor. KIR genes are tandemly arrayed over about 150 kb, with the remarkable feature that gene content varies between haplotypes. The discovery of KIR has also imparted an additional function on the human leukocyte antigen (HLA) class I molecules, which are encoded by genes within the major histocompatibility complex (MHC; chromosome 6). Through their interaction with KIR isotypes that inhibit natural killer (NK) cell activity, certain HLA class I molecules are now known to protect healthy cells from spontaneous destruction by NK-cell-mediated cytolysis. Other KIR isotypes stimulate the activity of NK cells. Thus, KIR are likely to play a significant role in the control of the immune response, which would explain the associations observed between certain KIR genes in rheumatoid arthritis, psoriatic arthritis and control of HIV disease progression. The degree of HLA/KIR compatibility may also determine the success rate of haematopoietic cell replacement therapy for certain leukemias.

Bookshelf ID: NBK10135
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