The leukocyte-associated Ig-like receptor-1 (LAIR-1) is a negative regulator of natural killer (NK) cells, its encoding gene belonging to the leukocyte receptor complex (LRC). Antibody to LAIR-1 can inhibit Ab-induced redirected lysis and TNF-alpha release of effector cells. LAIR-1 contains 2 immunoreceptor tyrosine-based inhibitory motifs (ITIM) in its cytoplasmic region that have been shown to bind constitutively and presumably regulate the tyrosine phosphatase SHP-1 in hematopoietic cells. SHP-1 mutation in mice results in abnormal lymphoproliferation, suggesting that LAIR-I may also be implicated in regulating hematopoiesis. Here we investigated a monoclonal antibody, 9.1C3, against a NK cell antigen previously described as inducing increased colony formation in in vitro assays of human bone marrow cells. We found that 9.1C3 was expressed on CD34 positive hematopoietic progenitors for the first time. In functional assays, 9.1C3 MAb was able to inhibit Ab-induced redirected lysis and TNF-alpha secretion of NK cells. We proved that 9.1C3 is identical to LAIR-1, based on the fact that not only the antigen precipitated by 9.1C3 MAb was of 40 kDa but also 9.1C3 MAb bound specifically to LAIR-1 cDNA transfected COS7 cells as well as recognized LAIR-I fusion protein in ELISA. This finding provided the first evidence that LAIR-1 expresses on hematopoietic progenitor, implicating its role in the regulation of hematopoiesis at early stage. (C) 2003 Elsevier Inc. All rights reserved.