To investigate the role of CD45 in rat NK cell function, we developed new m
Abs directed against rat CD45, mAb ANK12 binds to a high molecular isoform
of CD45 and mAb ANK74 binds to the common part on all known CD45 isoforms,
as has been described for the anti-rat CD45 mAb OX1. The ability of these m
Abs to affect NK cell-mediated lysis was tested using the Fc receptor-posit
ive target cell line P815, mAb ANK12 was found to significantly enhance the
lysis of P815, whereas ANK74 and the anti-CD45 mAb OX1 did not. In additio
n, cross-linking of the CD45 isoform by ANK12 induced tyrosine phosphorylat
ion of specific proteins in NK cells. Subsequently, the involvement of CD45
in the negative signaling after "self" MHC class I recognition by rat NK c
ells was investigated: The anti-CD45 mAbs were found to affect NK cell-medi
ated lysis of syngeneic tumor cell lines, depending upon the expression lev
el of MHC class I on target cells. mAbs ANK74 and OX1 only inhibited lysis
of the syngeneic tumor cell lines that expressed low levels of MHC class I.
Furthermore, both mAbs caused an inhibition of NK cell-mediated lysis of t
hese tumor cell lines when MHC class I molecules on the tumor cell lines we
re masked by an Ab, These results suggest that CD45 regulates the inhibitor
y signal pathway after self MHC class I recognition, supposedly by dephosph
orylation of proteins.