CD8αα homodimers function as a coreceptor for KIR3DL1

Significance Inhibitory receptors specific for major histocompatibility class I (MHC-I) molecules regulate NK cell responses. Here, we describe that cluster of differentiation 8αα (CD8αα) works as a coreceptor to enhance interaction between MHC-I and one of these receptors, KIR3DL1. We further demonstrate that inhibition of NK cell activation by MHC-I and KIR3DL1 interaction is fine-tuned by CD8αα. By testing cytokine secretion ability, we found CD8αα + NK cells are generally better educated, and thus more responsive to abnormal cells. All these results suggest that CD8αα is an important regulator of NK cell activation.