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The Journal of Immunology, 2000, 165: 6142-6147.
Copyright © 2000 by The American Association of Immunologists

Comparative Ability of Qdm/Qa-1b, Kb, and Db to Protect Class Ilow Cells from NK-Mediated Lysis In Vivo1

Song Hui Jia, Zoran Kurepa, Ailin Bai and James Forman2

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 {beta}2-microglobulin ({beta}2M) by a flexible linker (Qa-1 determinant modifier (Qdm)-{beta}2M). When this construct is expressed in TAP-2- or {beta}2M- cells, it allows for the expression of a Qdm-{beta}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-{beta}2M cells into C57BL/6 mice and measured their NK cell-mediated clearance from the lungs at 2 h. RMAS cells transfected with Qdm-{beta}2M were resistant to lung clearance, similar to RMA cells or RMAS cells in anti-asialo-GM1-treated mice, while untransfected or {beta}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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