Biology Reference
In-Depth Information
T A B L E
9.2. Properties of NK Subsets Sorted from HIV-Seropositive Donors
CD16
CD56
CD16
dim=
CD56
ÿ
K562 cytotoxicity
ADCC
TNF-a secretion
ÿ
IFN-g secretion
ÿ
Proliferation by IL-2
ÿ
CD69
Fas mRNA
ÿ
Hypodiploid DNA
ÿ
They were originally identi®ed in NK cells and have been shown to be respon-
sible for the ability of NK cells to discriminate between normal and abnormal
cells. Interaction between NK receptors and MHC molecules expressed in nor-
mal cells leads to inhibition of NK cell cytotoxicity. In humans, NK receptors
belong to three distinct molecular families namely, the Ig superfamily, and in-
clude several receptor molecules with two or three extracellular Ig-like domains
speci®c for HLA-C ( p58), HLA-B (p70), and HLA-A alleles ( p140). A second
group is formed by type II membrane molecules that are part of the C-type
lectin superfamily. They are formed by heterodimers formed by the covalent
association of CD94 and NKG2A. IL-15 and TGF-b have been shown to reg-
ulate the induction of CD94/NKG2A (Andre et al., 1999). These receptors are
speci®c for the nonclassical HLA molecules such as HLA-E. A third class with
Ig superfamily structure is represented by the LIR-1/ILT-2 molecules. They do
not bind to HLA-E but bind to various HLA-1 and act as promiscuous re-
ceptors for di¨erent HLA including HLA-G (De Maria and Moretta, 2000).
Despite the structural diversity of the three receptors, a common feature is a
characteristic sequence in the cytoplasmic domain of most of these receptors.
These receptors express the ITIM. Upon phosphorylation of the tyrosine
residue in these receptors, they bind the tyrosine phosphatases, SHP1 and/or
SHP2, that in turn terminate positive signals transmitted via other receptors
and thus inhibiting NK cell-mediated cytotoxicity or T-cell activation ( Lanier,
1998).
In humans, certain inhibitory NKR molecules with short cytoplasmic do-
mains and the NKG2C glycoprotein do not contain ITIM but have a lysine
residue in the transmembrane sequence. Several of these associate with a 16-kD
phosphoprotein that is expressed as a disul®de-bonded homodimer. A protein
of 12 kD was identi®ed and called DAP12 and is expressed as a disul®de
homodimer on dendritic cells, monocytes, granulocytes, NK cells, and the
subset of T cells. Upon ligation, it becomes tyrosine phosphorylated and is re-
sponsible for cell activation (Lanier et al., 1998).
A report by Galiani et al. (1999) reported the up-regulation of the expression
of KIRs in both T and NK cells in HIV-infected individuals. The KIRs in-
