Page 591 - Veterinary Immunology, 10th Edition

KIR Receptors
VetBooks.ir On the NK cells of humans, other primates, and cattle, the receptors

for MHC class I belong to a family of proteins called killer
inhibitory receptors (KIRs or CD158). KIRs may be either inhibitory
or stimulatory, but inhibitory receptors predominate. When these

inhibitory KIRs bind to MHC class I molecules on a target cell,
cytotoxicity is inhibited and healthy cells are not destroyed. Other
members of the KIR family may stimulate NK cell cytotoxicity, but
these receptors tend to have low binding affinities compared to the
inhibitory receptors, so this contributes to the dominance of

inhibition.
The human KIR gene locus is extremely polymorphic. Indeed,
allelic polymorphism is so extensive in this locus that it is difficult

to find unrelated individuals with identical KIR haplotypes. KIR
gene polymorphism affects sequences in the MHC class I binding
sites of these receptors, and as a result, it determines their binding
specificity. KIR gene expression patterns also vary clonally, so that
individual NK cells can express random combinations of KIR

receptors. This extreme diversity at the primate KIR locus results
from selection pressure analogous to that seen in MHC loci. In other
words, resistance to specific infections conferred by the KIR locus

will depend on an animal's haplotype. In addition to possessing
KIRs, cattle NK cells also have a diverse receptor repertoire based
on C-type lectin-like receptors, but it is unclear how this influences
KIR expression.
Although primate KIR genes vary in their number and diversity,

four are present in virtually all haplotypes and are called
framework loci. The total number of KIR genes expressed by a
single individual ranges between 7 and 12, depending on the

presence or absence of activating KIR loci. Other members of the
KIR family include the leukocyte immunoglobulin-like receptors
(LILRs) and NCR1 (NKp46, CD335). NCR1 (natural cytotoxicity
triggering receptor 1) is only expressed on NK cells, while the
LILRs are expressed on other leukocytes.

Ly49 Receptors

In rodents and horses, in contrast to humans and cattle, the
predominant NK cell MHC-binding receptors belong to the Ly49

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