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Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390
The class Ib molecule Qa-1b binds the class Ia leader
peptide, Qdm, which reacts with CD94/NKG2R on NK cells. We have
generated a gene that encodes the Qdm peptide covalently attached to
2-microglobulin (
2M) by a flexible linker
(Qa-1 determinant modifier (Qdm)-
2M). When this
construct is expressed in TAP-2- or
2M- cells, it allows for the expression of
a Qdm-
2M protein that associates with Qa-1b
to generate the Qdm epitope, as detected by
Qdm/Qa-1b-specific CTL. To test the biological significance
of expression of this engineered molecule, we injected
TAP-2- RMAS-Qdm-
2M cells into C57BL/6 mice
and measured their NK cell-mediated clearance from the lungs at 2
h. RMAS cells transfected with Qdm-
2M were resistant to
lung clearance, similar to RMA cells or RMAS cells in
anti-asialo-GM1-treated mice, while untransfected or
2M-transfected RMAS cells were rapidly cleared. Further,
pulsing RMAS cells with either Qdm, a Kb-, or
Db-binding peptide showed equivalent protection from
clearance, indicating that a single class Ia or Ib molecule can afford
complete protection from NK cells in this system. In contrast,
injection of RMAS cells into DBA/2 animals, which express low levels of
receptors for Qdm/Qa-1b, resulted in protection from lung
clearance if pulsed with a Kb- or Db-binding
peptide, but not the Qa-1b-binding peptide,
Qdm.
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