Lectin-like Transcript Research Articles

Characterization of the Chicken C-Type Lectin-Like Receptors B-NK and B-lec Suggests That the NK Complex and the MHC Share a Common Ancestral Region

The sequencing of the chicken MHC led to the identification of two open reading frames, designated B-NK and B-lec, that were predicted to encode C-type lectin domains. C-type lectin domains are not encoded in the MHC of any animal described to date; therefore, this observation was completely unexpected, particularly given that the chicken has a "minimal essential MHC." In this study, we describe the initial characterization of the B-NK and B-lec genes, and show that they share greatest homology with C-type lectin-like receptors encoded in the human NK complex (NKC), in particular NKR-P1 and lectin-like transcript 1 (LLT1), respectively. In common with NKR-P1 and LLT1, B-NK and B-lec are located next to each other and transcribed in opposite orientation. Like human NKR-P1, B-NK has a functional inhibitory signaling motif in the cytoplasmic tail and is expressed in NK cells. In contrast, B-lec contains an endocytosis motif in the cytoplasmic tail, and like LLT1, is an early activation Ag. Further analysis leads us to propose that there are four subgroups of C-type lectin-like receptors in the NKC, which arose as a result of duplication events. Moreover, this analysis suggests that the NKC may be considered a fifth paralogous region, and therefore shares an ancient common origin with the MHC. This provides evidence that C-type lectin-like receptors were present in the preduplication, primordial MHC region, and suggests that an original function of MHC molecules was for recognition by NK cell receptors encoded nearby.

The LLT1 receptor induces IFN-γ production by human natural killer cells

Natural killer cell functions are regulated by signals through activating and inhibitory receptors. These receptors belong to the immunoglobulin superfamily or the lectin superfamily. We have previously identified a lectin-like transcript, LLT1, expressed in human NK cells. In the present study, we have generated a monoclonal antibody, L9.7, that specifically binds LLT1 receptor and studied the functional role of LLT1 in human NK cells. Binding of mAb L9.7 to surface LLT1 induced IFN-γ production, but did not modulate cytotoxicity by YT cells, a human NK cell line. We further demonstrate that in resting NK cells as well as in IL-2 activated NK cells LLT1 induced IFN-γ production, but not cytotoxicity. Excess amounts of L9.7 mAb failed to increase natural or antibody-dependent cell-mediated cytolytic activity, whereas minimal amounts achieved maximal production of IFN-γ by YT and activated NK cells. These findings further support the separation of signaling pathways that regulate cytotoxicity and IFN-γ production in resting as well as activated NK cells.

Differentially induced expression of C-type lectins in activated lymphocytes.

The human NK gene complex encodes for the leucocyte C-type lectins, CD69, AICL (activation-induced C-type lectin), LLT1 (lectin-like transcript), CD161/NKR-P1A, CD94, and for NKG-2 molecules. These gene products have been implicated in the regulation of the function of natural killer (NK) cells and other lymphocytes. In this study the expression of C-type lectins during the early activation of PMA-stimulated peripheral blood lymphocytes was examined. To investigate the influence of de novo protein synthesis on activation-dependent expression of C-type lectins, cells were cultured in presence of cycloheximide (CHX) and mRNA levels were analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Upregulated levels of CD69, AICL, and LLT1, but less pronounced changes of CD161/NKR-P1A and CD94 mRNA were found at early time points of cellular activation. CD69 was superinduced by CHX at the nuclear precursor transcript and the mRNA level suggesting that regulation of transcriptional activity and mRNA stability contribute to extent of CD69 mRNA accumulation. CHX treatment resulted also in an overexpression of AICL, LLT1, and CD161/NKR-P1A mRNAs. Conversely, CHX blocked CD94 mRNA expression in PMA-stimulated cells, demonstrating that this process is dependent on new protein synthesis. Expression kinetics in context with susceptibility to CHX indicate that the mechanisms responsible for upregulated CD69, AICL, and LLT1 expression are distinct from those which control CD161/NKR-P1A or CD94 expression. J. Cell. Biochem. Suppl. 36: 201-208, 2001.

Cloning of a new lectin-like receptor expressed on human NK cells.

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 in lethally irradiated animals. A large family of NK cell receptors belong to the C-type lectin superfamily and are localized to the NK gene complex on Chromosome (Chr) 6 in the mouse and Chr 12 in the human. Genes in the NK gene complex encode 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 and chromosomal mapping of a human lectin-like transcript (LLT1) expressed on NK, T, and B cells and localized to the NK gene complex within 100 kilobases 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 132 amino acid residues with similarity to the carbohydrate recognition domain of C-type lectins. The predicted protein of LLT1 shows 59 and 56% similarity to AICL and CD69, respectively. The predicted protein does not contain any intracellular ITIM motifs, suggesting that LLT1 may be involved in mediating activation signals.