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The Novel Inhibitory NKR-P1C Receptor and Ly49s3 Identify Two Complementary, Functionally Distinct NK Cell Subsets in Rats¹

Lise Kveberg^*, Camilla J. Bäck^*, Ke-Zheng Dai, Marit Inngjerdingen^*, Bent Rolstad^*, James C. Ryan, John T. Vaage^2, and Christian Naper

^* Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway; and Veterans Affairs Medical Center, Northern California Institute for Research and Education and University of California, San Francisco, CA 94121

The proximal region of the NK gene complex encodes the NKR-P1 family of killer cell lectin-like receptors which in mice bind members of the genetically linked C-type lectin-related family, while the distal region encodes Ly49 receptors for polymorphic MHC class I molecules. Although certain members of the NKR-P1 family are expressed by all NK cells, we have identified a novel inhibitory rat NKR-P1 molecule termed NKR-P1C that is selectively expressed by a Ly49-negative NK subset with unique functional characteristics. NKR-P1C⁺ NK cells efficiently lyse certain tumor target cells, secrete cytokines upon stimulation, and functionally recognize a nonpolymorphic ligand on Con A-activated lymphoblasts. However, they specifically fail to kill MHC-mismatched lymphoblast target cells. The NKR-P1C⁺ NK cell subset also appears earlier during development and shows a tissue distribution distinct from its complementary Ly49s3⁺ subset, which expresses a wide range of Ly49 receptors. These data suggest the existence of two major, functionally distinct populations of rat NK cells possessing very different killer cell lectin-like receptor repertoires.