Abstracts (complete list) - Wissenschaft Online

Maren Claus, Sabine Wingert, Carsten Watzl
NK cell activity is regulated by CD48 - 2B4 (CD244)
interaction in cis and in trans
Function of human NK cells is regulated by a variety of different cell surface receptors.
SLAM-related receptors (SRR) are important modulators of NK cell activity. Most SRR
are activated by homophilic interaction. Thus, SRR do not only function as activating NK
cell receptors, but also as activating NK cell ligands. 2B4 (CD244) is the only SRR that is
activated by binding to a distinct ligand: CD48 is a GPI-anchored surface molecule that
is widely expressed on hematopoietic cells. Recent work demonstrated that, like other
SRR, 2B4 expressing target cells can also induce NK cell cytotoxicity by interacting with
NK cell expressed CD48. These findings suggest an additional function of the 2B4-ligand
CD48 as an activating receptor on NK cells.
In the present study, we show that 2B4 does not only bind in trans to CD48 on
neighboring cells, but can also interact in cis with CD48 molecules on the same NK cell,
thereby modulating NK cell activity. The expression level of CD48 on NK cells is about
20fold higher than that of 2B4. Using soluble CD48-ILZ fusion proteins, we demonstrate
that removal of endogenous CD48 from the cell surface by phosphatidylinositol-specific
phospholipase C (PI-PLC) increases the binding of soluble CD48 to NK cell 2B4. This
suggests that the interaction between CD48 and 2B4 in cis prevents the 2B4 receptor
from recognizing CD48 in trans. To test if this also has functional consequences we
decreased the density of CD48 on the cell surface of NK92 cells by PI-PLC treatment.
This significantly increased 2B4-mediated cytotoxicity against CD48 expressing target
cells. Taken together, our findings provide evidence for the modulation of NK cell
activity by the density of 2B4 and CD48 on both the NK cell and the potential target
cell. Further, the present data suggest functional consequences of an in cis interaction
between 2B4 and CD48 for NK cell activity.