We describe the characterization of sialic acid-binding Ig-like lectin-7 (siglec-7), a novel member of the siglec subgroup of the immunoglobulin superfamily. A full-length cDNA encoding siglec-7 was isolated from a human primary dendritic cell cDNA library. Siglec-7 is predicted to contain three extracellular immunoglobulin-like domains that comprise an N-terminal V-set domain and two C2-set domains, a transmembrane region and a cytoplasmic tail containing two tyrosine residues embodied in immunoreceptor tyrosine-based inhibition motif-like motifs. Overall, siglec-7 exhibited a high degree of sequence similarity to genes encoding CD33 (siglec-3), siglec-5, OBBP1/siglec-6, and OBBP-like protein and mapped to the same region on chromosome 19q13.3. When siglec-7 was expressed on COS or Chinese hamster ovary cells, it was able to mediate high levels of sialic acid-dependent binding to human erythrocytes and soluble sialoglycoconjugates, suggesting that it may be involved in cell-cell interactions. Among human peripheral blood leukocytes, siglec-7 was found to be present at low levels on granulocytes, intermediate levels on monocytes, and relatively high levels on a major subset of natural killer cells and a minor subset of CD8 ؉ T cells. Immunoprecipitation experiments indicated that siglec-7 is expressed as a monomer of ϳ65 kDa.

Siglec-7 is a sialic acid binding receptor with inhibitory potential, expressed on human NK cells and monocytes. It has an unusual binding preference for § 2,8-linked disialic acids, such as those displayed by ganglioside GD3. Here we have investigated whether siglec-7-GD3 interactions are able to modulate NK cell cytotoxicity. Using synthetic polyacrylamide glycoprobes, siglec-7 was found to be masked at the NK cell surface but it could be unmasked by sialidase treatment of NK cells. GD3 synthase-transfected P815 target cells expressed high levels of GD3 and bound strongly to recombinant siglec-7-Fc protein. Surprisingly, GD3 synthase-transfected P815 cells were killed more effectively by untreated cells in a siglec-7-independent manner. However, following sialidase treatment of NK cells, a siglec-7-dependent inhibition of killing was observed. These findings have important implications for NK cell cytotoxicity against tumor cells like melanoma that express high levels of GD3 ganglioside.

Here we characterize the properties and expression pattern of Siglec-9 (sialic acid-binding Ig-like lectin-9), a new member of the Siglec subgroup of the immunoglobulin superfamily. A full-length cDNA encoding Siglec-9 was isolated from a dibutyryl cAMP-treated HL-60 cell cDNA library. Siglec-9 is predicted to contain three extracellular immunoglobulin-like domains that comprise an N-terminal V-set domain and two C2-set domains, a transmembrane region and a cytoplasmic tail containing two putative tyrosine-based signaling motifs. Overall, Siglec-9 is ϳ80% identical in amino acid sequence to Siglec-7, suggesting that the genes encoding these two proteins arose relatively recently by gene duplication. Binding assays showed that, similar to Siglec-7, Siglec-9 recognized sialic acid in either the ␣2,3-or ␣2,6-glycosidic linkage to galactose. Using a specific mAb, Siglec-9 was found to be expressed at high or intermediate levels by monocytes, neutrophils, and a minor population of CD16 Sialic acid-binding immunoglobulin-like lectins (Siglecs) 1 are transmembrane sialic acid-binding proteins of the immunoglobulin (Ig) superfamily characterized by the presence of an N-terminal V-set Ig-like domain and variable numbers of C2 set domains (1). The first Siglecs to be characterized were sialoadhesin/Siglec-1, CD22/Siglec-2, CD33/Siglec-3 and myelin-associated glycoprotein/Siglec-4 which share ϳ25-30% sequence identity within the extracellular regions (2). Recent studies (3-8) have uncovered the existence of a cluster of genes on human chromosome 19q13.3-4 that encode novel Siglecs highly related to CD33. This CD33-related subgroup includes Siglecs-3, -5, -6, -7, and -8, each of which share ϳ50 -70% sequence identity, suggesting that the genes encoding them have arisen relatively recently by gene duplication and exon shuffling. Despite their sequence similarity, all novel Siglecs characterized to date are expressed on distinct subsets of hemopoietic cells, such as neutrophils (Siglec-5) (4), B cells (Siglec-6) (8), natural killer (NK) cells (Siglec-7) (5, 6), and eosinophils (Siglec-8) (7). Each of these Siglecs also exhibits distinct carbohydrate binding properties (4, 5, 7-10). These differences in expression and ligand binding suggest that each Siglec mediates a specific, nonredundant function in hemopoietic cell biology.The cytoplasmic tails of most CD33-related Siglecs contain two homologous tyrosine-based motifs, one of which fits the consensus for immune receptor tyrosine-based inhibitory motifs (ITIMs) (11). The presence of one or more ITIMs has been described in a growing number of other leukocyte membrane receptors, many of which are tightly linked to CD33-related Siglecs on chromosome 19q13.4, in a region known as the leukocyte receptor cluster (12). The consensus that has emerged is that receptors bearing ITIMs mediate inhibitory functions when co-cross-linked with activating receptors bearing tyrosine based activatory motifs (reviewed in Ref. 11). This has been shown to be due to tyrosine phosphorylation of t...

This study is the most comprehensive characterization of S. haematobium antigens to date and describes novel antigens in all schistosome species. Posttreatment results are consistent with praziquantel treatment inducing quantitative and qualitative changes in schistosome-specific antibody responses.

Here we characterize Siglec-10 as a new member of the Siglec family of sialic acid-binding Ig-like lectins. A full-length cDNA was isolated from a human spleen library and the corresponding gene identified. Siglec-10 is predicted to contain five extracellular Ig-like domains and a cytoplasmic tail containing three putative tyrosine-based signalling motifs. Siglec-10 exhibited a high degree of sequence similarity to CD33-related Siglecs and mapped to the same region, on chromosome 19q13.3. The expressed protein was able to mediate sialic acid-dependent binding to human erythrocytes and soluble sialoglycoconjugates. Using specific antibodies, Siglec-10 was detected on subsets of human leucocytes including eosinophils, monocytes and a minor population of natural killer-like cells. The molecular properties and expression pattern suggest that Siglec-10 may function as an inhibitory receptor within the innate immune system.