Comparative ability of Qdm/Qa-1b, Kb, and Db to protect class I(low) cells from NK-mediated lysis in vivo

S. H. Jia, Z. Kurepa, A. Bai, J. Forman

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 β2-microglobulin (β2M) by a flexible linker (Qa-1 determinant modifier (Qdm)-β2M). When this construct is expressed in TAP-2- or β2M- cells, it allows for the expression of a Qdm-β2M protein that associates with Qa-1b to generate the Qdm epitope, as detected by Qdm/Qa1b-specific CTL. To test the biological significance of expression of this engineered molecule, we injected TAP-2- RMAS-Qdm-β2M cells into C57BL/6 mice and measured their NK cell-mediated clearance from the lungs at 2 h. RMAS Cells transfected with Qdm-β2M were resistant to lung clearance, similar to RMA Cells or RMAS cells in anti-asialo-GM1-treated mice, while untransfected or β2M-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.

Original languageEnglish (US)
Pages (from-to)6142-6147
Number of pages6
JournalJournal of Immunology
Volume165
Issue number11
StatePublished - Dec 1 2000

Fingerprint

Natural Killer Cells
Peptides
Lung
Protein Sorting Signals
Inbred C57BL Mouse
Epitopes
Injections
Genes
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Comparative ability of Qdm/Qa-1b, Kb, and Db to protect class I(low) cells from NK-mediated lysis in vivo. / Jia, S. H.; Kurepa, Z.; Bai, A.; Forman, J.

In: Journal of Immunology, Vol. 165, No. 11, 01.12.2000, p. 6142-6147.

Research output: Contribution to journalArticle

@article{c69695ac436d4827b93947b6050974f0,
title = "Comparative ability of Qdm/Qa-1b, Kb, and Db to protect class I(low) cells from NK-mediated lysis in vivo",
abstract = "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 β2-microglobulin (β2M) by a flexible linker (Qa-1 determinant modifier (Qdm)-β2M). When this construct is expressed in TAP-2- or β2M- cells, it allows for the expression of a Qdm-β2M protein that associates with Qa-1b to generate the Qdm epitope, as detected by Qdm/Qa1b-specific CTL. To test the biological significance of expression of this engineered molecule, we injected TAP-2- RMAS-Qdm-β2M cells into C57BL/6 mice and measured their NK cell-mediated clearance from the lungs at 2 h. RMAS Cells transfected with Qdm-β2M were resistant to lung clearance, similar to RMA Cells or RMAS cells in anti-asialo-GM1-treated mice, while untransfected or β2M-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.",
author = "Jia, {S. H.} and Z. Kurepa and A. Bai and J. Forman",
year = "2000",
month = "12",
day = "1",
language = "English (US)",
volume = "165",
pages = "6142--6147",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Comparative ability of Qdm/Qa-1b, Kb, and Db to protect class I(low) cells from NK-mediated lysis in vivo

AU - Jia, S. H.

AU - Kurepa, Z.

AU - Bai, A.

AU - Forman, J.

PY - 2000/12/1

Y1 - 2000/12/1

N2 - 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 β2-microglobulin (β2M) by a flexible linker (Qa-1 determinant modifier (Qdm)-β2M). When this construct is expressed in TAP-2- or β2M- cells, it allows for the expression of a Qdm-β2M protein that associates with Qa-1b to generate the Qdm epitope, as detected by Qdm/Qa1b-specific CTL. To test the biological significance of expression of this engineered molecule, we injected TAP-2- RMAS-Qdm-β2M cells into C57BL/6 mice and measured their NK cell-mediated clearance from the lungs at 2 h. RMAS Cells transfected with Qdm-β2M were resistant to lung clearance, similar to RMA Cells or RMAS cells in anti-asialo-GM1-treated mice, while untransfected or β2M-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.

AB - 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 β2-microglobulin (β2M) by a flexible linker (Qa-1 determinant modifier (Qdm)-β2M). When this construct is expressed in TAP-2- or β2M- cells, it allows for the expression of a Qdm-β2M protein that associates with Qa-1b to generate the Qdm epitope, as detected by Qdm/Qa1b-specific CTL. To test the biological significance of expression of this engineered molecule, we injected TAP-2- RMAS-Qdm-β2M cells into C57BL/6 mice and measured their NK cell-mediated clearance from the lungs at 2 h. RMAS Cells transfected with Qdm-β2M were resistant to lung clearance, similar to RMA Cells or RMAS cells in anti-asialo-GM1-treated mice, while untransfected or β2M-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.

UR - http://www.scopus.com/inward/record.url?scp=0034541215&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034541215&partnerID=8YFLogxK

M3 - Article

VL - 165

SP - 6142

EP - 6147

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -