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*
Laboratory of Experimental Immunology, Division of Basic Sciences, and
Intramural Research Support Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702;
University of Oklahoma, Health Sciences Center, Oklahoma City, OK 73104; and
§
Laboratory of Biological Chemistry, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224.
Murine NK cells express Ly-49 family receptors capable of either
inhibiting or activating lytic function. The overlapping patterns of
expression of the various receptors have complicated their precise
biochemical characterization. Here we describe the use of the Jurkat T
cell line as the model for the study of Ly-49s. We demonstrate that
Ly-49D is capable of delivering activation signals to Jurkat T cells
even in the absence of the recently described Ly-49D-associated chain,
DAP-12. Ly-49D signaling in Jurkat leads to tyrosine phosphorylation of
TCR
and requires Syk/Zap70 family kinases and arginine 54 of Ly-49D,
suggesting that Ly-49D signals via association with TCR.
Coexpression studies in 293-T cells confirmed the ability of Ly-49D to
associate with TCR. In addition, we have used this model to study
the functional interactions between an inhibitory Ly-49 (Ly-49G2) and
an activating Ly-49 (Ly-49D). Ly-49G2 blocks activation mediated by
Ly-49D in an immunoreceptor tyrosine-based inhibitory motif
(ITIM)-dependent manner. In contrast, Ly-49G2 was incapable of
inhibiting activation by the TCR even though human killer cell
inhibitory receptor (KIR) (KIR3DL2(GL183)) effectively inhibits TCR.
Both the ability of Ly-49G2 to block Ly-49D activation and the failure
of Ly-49G2 to inhibit TCR signaling were confirmed in primary murine NK
cells and NK/T cells, respectively. These data demonstrate the dominant
effects of the inhibitory receptors over those that activate and
suggest an inability of the Ly-49 type II inhibitory receptors to
efficiently inhibit type I transmembrane receptor signaling in T cells
and NK cells.
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