Raising primary antibodies against the carbohydrates themselves has historically been problematic with so many carbohydrate structures being involved in immune signalling pathways when antibody technologies were being initially developed, since glycosylation influences the function of all immune cells. Glycans play a crucial role in intercellular contacts and leukocytes migration. These interactions are important in activation and proliferation of leukocytes and during immune response.(4)
With the advent of antibody engineering techniques, the first anti-glycan antibodies are reaching the market. Although there are limited numbers currently commercially available, they offer the benefit of carbohydrate specific binding with the familiarity of IgG antibodies, for which much more is known as therapeutic entities than lectins. Currently available antibodies include those against Stage-specific embryonic antigen-4 (SSEA-4), whose expression changes both qualitatively and quantitatively during development, differentiation and in tumorigenesis, and 3’-Sulfo-Lewis X (3-SLeX), a glycan epitope that has been reported to act as a ligand for the adhesion molecules E- and L-selectin which may help identify tumours with higher likelihood of progression and metastasis. Glykogen has further antibodies in development including antibodies specific for SSEA3 and GloboH.
SigLecs are sialic acid binding ImmunoGlobulin-type Lectins – a whole family of proteins expressed by cells of the immune system - that are sensitive to variations in the presentation of sialic acid and it is suggested that different immune responses can be generated based on the Sialic acid linkage detected.
Lectins can have a number of sugar recognition sites, with the binding affinity increasing with the number of correct matches between the lectin and the carbohydrate, which also relies on the spatial presentation of the sugars. The strength of the binding of a lectin to a sugar can therefore also help to distinguish between different isotypes of carbohydrate that would appear the same on a mass spectrometer.
Of themselves, lectins are a study area of interest. Some of the well-characterized roles of lectins are in cell-cell communication, cancer metastasis, embryogenesis, host-pathogen interactions, and tissue development (5).