Page 592 - Veterinary Immunology, 10th Edition

family of glycoproteins. They have the same function as KIR
VetBooks.ir receptors in that they bind MHC class I molecules and are

exceptionally polymorphic. There are at least 23 members (Ly49A
to Ly49W) in this family in mice. All are homodimeric type II

transmembrane C-type lectins. Ly49 haplotypes also contain
variable numbers of inhibitory and activating genes, some of which
can recognize MHC class I molecules. Horses and donkeys have at
least five highly conserved Ly49 genes. Unlike mice and horses,

humans, pigs, dogs, cats and cattle possess only a single Ly49-like
gene. This is a pseudogene in humans but may be functional in
cattle. NK1.1 is a member of the Ly49 family that acts as an
activating receptor on mouse NK cells.

NKG2 Receptors

The third family of MHC-binding receptors on NK cells are
activating molecules that belong to the NKG2 receptor system.
NKG2D receptors bind to nonclassical MHC class I proteins
produced by stressed cells. Two of the most important of these

ligands are polymorphic MHC class I-like molecules called MIC-A
(major histocompatibility complex, class I chain-related A) and
MIC-B coded for by MHC class Ic genes (Chapter 11). Unlike

conventional class I molecules, these do not bind antigenic
peptides. While minimally expressed on normal, healthy cells, they
are expressed in large amounts by stressed cells. These stresses may
include DNA damage due to ionizing radiation or alkylating
agents, heat shock, and oxidative stress. MIC-A and MIC-B are

overexpressed in tumor cells and virus-infected cells. When these
ligands bind to NKG2D, it overrides the inhibitory effects of
conventional MHC class I molecules and triggers NK cytotoxicity.

NKG2D is also expressed on activated γ/δ and α/β T cells,
suggesting that they too have a role in innate immunity. It may be
that the combination of γ/δ T cells and NK cells kills tumors on
surfaces, whereas a combination of α/β T cells and NK cells is most
effective within the body.

Fc Receptors

NK cells also recognize and kill target cells using an antibody-
dependent pathway employing the Fc receptor, CD16 (FcγRIII).

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