Participation of the CD94 receptor complex in costimulation of human natural killer cells

Stephan D. Voss, John Daley, Jerome Ritz, Michael J. Robertson

Research output: Contribution to journalArticle

65 Scopus citations


Optimal proliferation and expansion of human NK cells require mitogenic cytokines together with cell contact-dependent costimulation. Production of mAb that can modulate human NK cell proliferation yielded NKH3, which recognizes the CD94 Ag. NKH3 immunoprecipitates contain ~70-kDa heterodimeric complexes consisting of a ~25-kDa glycoprotein and ~40- to 45-kDa molecules. Analysis by two-dimensional isoelectric focusing/SDS-PAGE suggests that several different 40- to 45-kDa species are present in the CD94 receptor complex in human NK cells. NKH3 reacted with essentially all resting NK cells, although CD94 is expressed at higher levels on the CD56(bright) (i.e., high level of CD56) CD16(dim/neg) (i.e., low level of or absent CD16) subpopulation than on the more abundant CD56(dim)CD16(bright) NK cell subset. Moreover, the Z199 mAb, which appears to recognize NKG2-A species that can form heterodimers with CD94, stained virtually all CD56(bright) NK cells, but only a subset of CD56(dim) NK cells. Ligation of CD94 augmented the proliferation of CD56(bright) NK cells in response to IL-2 or IL-15 by as much as 10-fold. Secretion of IFN-γ by CD56(bright) NK cells stimulated with IL-2 or IL-15 was also enhanced up to 10-fold after CD94 ligation. CD94 mAb did not consistently costimulate proliferation of or IFN-γ production by CD56(dim) NK cells cultured with IL-2 or IL-15. In contrast, irradiated K562 cells costimulated proliferation of both CD56(bright) and CD56(dim) NK cells. These results indicate that CD56(bright) and CD56(dim) NK cells can be costimulated through different receptors, which may allow these distinct NK cell subsets to be independently regulated in vivo.

Original languageEnglish (US)
Pages (from-to)1618-1626
Number of pages9
JournalJournal of Immunology
Issue number4
StatePublished - Feb 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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