We previously provided the first characterization of the human activating C-type lectin-like receptor (CTLR) NKp65. Like its close relative NKp80, NKp65 is a homodimeric CTLR with a cytoplasmic hemITAM-like signaling motif and encoded in the Natural Killer Gene Complex (NKC) juxtaposed to its ligand. While NKp80 ligates AICL expressed by myeloid cells, NKp65 was found to be a high-affinity receptor for KACL, like AICL a member of the human CLEC2 family of CTLR. Strikingly, KACL expression is almost exclusively confined to human skin, i.e. keratinocytes. NKp65/KACL interaction has been shown to activate cytotoxicity and IFNg secretion of an NKp65- expressing NK cell line. However, while NKp80 is expressed by virtually all human NK cells, physiological expression of NKp65 remained enigmatic. In order to identify NKp65 expressing cells we generated NKp65-specific mAb that specifically stain a small subset of human innate lymphocytes isolated from peripheral blood. Transcriptional profiling of NKp65-expressing cells suggested that NKp65 expression is associated with a distinct subset of innate lymphocytes. Phenotypic analyses confirmed exclusive expression of NKp65 on this innate lymphocytes subset, while no NKp65 expression on NK cells was observed. Hence NKp65 hallmarks this subset of innate lymphocytes and may endow this subset with the capacity for dedicated immunosurveillance of human skin.
- Copyright © 2013 by The American Association of Immunologists, Inc.