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Good afternoon. I'm Mary Carrington and I will present a talk describing the influence of
variation at the killer cell immunoglobulin-like receptor gene complex on human disease.
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Natural killer cells express killer cell immunoglobulin-like receptors or KIR on
their cell surface that can confer either
activating or inhibitory signals to the NK cell.
Inhibitory KIR recognize specific allotypes of HLA class I on potential targets,
and if these ligands are present on a target cell,
the inhibitory KIR will send a signal not to kill that target
because it is normal in terms of HLA class I expression.
Some virally infected cells and some tumor cells down-regulate
HLA class I in order to escape cytotoxic T cell recognition.
In this case, the inhibitory KIR will not see its ligand in the normal context,
and an activating receptor,
which can be an activating KIR,
can now send a signal to kill that target
as it is aberrant in terms of class I expression.
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The nomenclature for the KIR genes and molecules
is based on the number of extracellular domains,
termed 2D or 3D, and whether the molecule has a long or short cytoplasmic tail.
On the far left are three domain long-tailed KIR termed KIR 3DL.
On the far right is a three domain short-tailed KIR termed KIR 3DS.
In general, the long-tailed KIR are inhibitory and the short-tailed KIR are activating.
The genes encoding ligands for KIR are the HLA class I genes which map to the MHC,
