The nonclassical major histocompatibility complex molecule Qa-2 protects tumor cells from NK cell- and lymphokine-activated killer cell-mediated cytolysis

Eugene Y. Chiang, Maile Henson, Iwona Stroynowski

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The cytotoxic activity of NK cells is regulated by class I MHC proteins. Although much has been learned about NK recognition of class I autologous targets, the mechanisms of NK self-tolerance are poorly understood. To examine the role of a nonpolymorphic, ubiquitously expressed class Ib Ag, Q9, we expressed it on class I-deficient and NK-sensitive B78H1 melanoma. Presence of this Qa-2 family member on tumor cells partially protected targets from lysis by bulk lymphokine-activated killer (LAK) cells. H-2Kb-expressing B78H1 targets also reduced LAK cell activity, while H-2Db offered no protection. Importantly, blocking with F(ab1)2 specific for Q9 or removal of this GPI-attached molecule by phospholipase C cleavage restored killing to the level of vector-transfected cells. Experiments with LAK cells derived from H2b SCID and B6 mice established that NK1.1+TCR- NK and NK1.1+TCR+ LAK cells were the prevalent cytolytic populations inhibitable by Q9. Treatment of mice with poly(I:C) also resulted in generation of Q9-regulated splenic cytotoxicity. LAK cells from different mouse strains responded to Q9, suggesting that the protective effect of this molecule is not detectably influenced by Ly49 polymorphisms or the presence/absence of Q9 in NK-harboring hosts. We propose that Q9 expressed on melanoma cells serves as a ligand for yet unidentified NK inhibitory receptor(s) expressed on NK1.1+ NK/T cells.

Original languageEnglish (US)
Pages (from-to)2200-2211
Number of pages12
JournalJournal of Immunology
Volume168
Issue number5
DOIs
StatePublished - Mar 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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