In the mouse, at least three members of the Klrb (Killer cell lectin-like receptor, subfamily b; formerly NKR-P1) gene family have been identified (Klrb1a/NKR-P1A, Klrb1b/NKR-P1B, and Klrb1c/NKR-P1C); but in the human gene family, a single homologue has been designated KLRB1, NKR-P1A, or CD161. The KLRB1/NKR-P1 family of proteins are type-II-transmembrane C-type lectin receptors. KLRB1C/NKR-P1C activates NK-cell cytotoxicity, while KLRB1B/NKR-P1B functions as an inhibitory receptor. KLRB1B/NKR-P1B protein has intracellular Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM), while KLRB1C/NKR-P1C lacks ITIM and activates via association with Fc Receptor γ chain. Strikingly, KLRB1B/NKR-P1B and KLRB1C/NKR-P1C share 96% amino acid sequence identity in their extracellular C-type lectin domains. The PK136 antibody reacts with the NK-1.1 surface antigen (CD161c) encoded by the Klrb1c/NKR-P1C gene expressed on natural killer (NK) cells in selected strains of mice (eg, C57BL, FVB/N, NZB, but not A, AKR, BALB/c, CBA/J, C3H, C57BR, C58, DBA/1, DBA/2, NOD, SJL, 129) and the CD161b antigen encoded by the Klrb1b/NKR-P1B gene expressed only on Swiss NIH and SJL mice, but not on C57BL/6. Expression of KLRB1C/NKR-P1C protein is correlated with the ability to lyse tumor cells in vitro and to mediate rejection of bone marrow allografts. The NK-1.1 marker is useful in defining NK cells; however, the antigen is also expressed on a rare, specialized population of T lymphocytes (NK-T cells) and some cultured monocytes. Plate-bound PK136 mAb, in combination with low concentrations of IL-2, induces proliferation of a subset of NK cells.