| 摘要 |
Natural killer (NK) cells constitute the third major population of lymphocytes. They possess the inherent capacity to kill various tumor and virally infected cells and mediate the rejection of bone marrow grafts. A large family of NK cell receptors belong to the C-type lectin family and are localized to NK gene complex on chromosome 6 or 12 in the mouse or human, respectively. Genes in the NK gene complex are all type II receptors and examples include the families of NKR-P1, Ly-49, and NKG2 receptors. Examples of other C-type lectin-like NK cell receptors that occur as individual genes are CD94, CD69, and AICL. Here we report the molecular characterization of a human lectin-like transcript (LLT1) expressed on NK, T, and B cells and localized to the NK gene complex within 100 kb of CD69. The cDNA encodes a predicted protein of 191 amino acid residues with a transmembrane domain near the N-terminus and an extracellular domain of 131 amino acid residues with homology to the carbohydrate recognition domain of C-type lectins. The predicted protein of LLT1 shows 59 and 56% similarity to AICL and CD69 respectively. We generated a monoclonal antibody (L9.7) against LLT1 and analyzed the functional role of LLT1 in NK cells. Binding of mAb L9.7 induced IFN-g production, but did not modulate cytotoxicity by YT cells, a human NK cell line. We further demonstrate that LLT1 receptor functions as an activating receptor for cytokine production (IFN-g) in resting as well as in IL-2 activated NK cells. Excess amounts of L9.7 mAb failed to increase direct or rADCC cytolytic activity, whereas minimal amounts achieved maximal production of IFN-g by YT and activated NK cells. LLT1 is the first receptor identified that regulate IFN-g production but not cytotoxicity in NK cells.
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