NKG2D transmits stimulatory signals to natural killer cells and other hematopoietic cells, leading to enhanced proliferation, cytokine secretion and target killing. Murine and human NKG2D each recognize five known class I-related molecules with distinct primary structures. Here, we used surface plasmon resonance to examine the binding of murine NKG2D to its cognate ligands: RAE-1B6 (a newly described C57BL/6J variant of RAE-1), RAE-1δ (common to BALB and C57BL6/J), and H60 (expressed in BALB, but not C57BL/6J). While RAE-1B6 and H60 display relatively high affinities for NKG2D with KD in the 20-30 nM range and koff in the 0.03 s-1 to 0.06 s-1 range (t1/2 approximately 10-20 s); the RAE-1δ variant binds with a lower affinity: KD of approximately 750 nM. Furthermore, RAE-1δ displays biphasic kinetics with dominant koff of approximately 0.2 s-1 (t1/2 approximately 3 s), partially explaining the lower affinity. Thus, H60 and RAE-1B6 bind NKG2D with almost identical kinetics while sharing only 20% amino acid sequence identity; whereas other RAE-1 molecules demonstrate faster dissociation and lower affinities than RAE-1B6 despite sharing 90% sequence identity. C57BL/6J mice, although not expressing the H60 gene product, retain a high-affinity ligand for NKG2D in the form of RAE-1B6.

Original languageEnglish
Pages (from-to)597-605
Number of pages9
JournalEuropean Journal of Immunology
Issue number3
StatePublished - 2002


  • Affinity
  • Immunological receptor
  • Kinetics
  • NK cell
  • Surface plasmon resonance


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