The biological effects of various plant lectins have been extensively investigated over the last 30 years. This interest was stimulated by initial findings made in 60s that some lectins are able to induce proliferation of human and animal lymphocytes. It was demonstrated that in parallel with their mitogenic ability lectins were able to induce the cytotoxic activity in T lymphocytes. Lectin-induced cytotoxicty of T lymphocytes was found to be antigen nonspecific and directed against various normal and malignant cells. The mechanisms of lectindependent cell-mediated cytotoxicity (LDCC) was recently clarified and was found to be due to the ability of some lectins to bind and activate the T-cell receptor and trigger the intracellular signaling with activation of various genes resulting in production of various lymphokines. Some lectins were found to be directly cytotoxic and lysed various normal or malignant cells in the absence of lymphocytes. The mechanisms responsible for this direct lectin cytotoxicity remain unclear. Some experimental data indicate that lectins are able to kill cells via the induction of programmed cell death (apoptosis). This review will summarize studies of cytotoxic activities of lectins, mechanisms of their cytotoxicity and analyze possible biological significance of lectin cytotoxicity in humans and animals.
Recently several authors have reported that T lymphocyte activation induces important changes in glycosylation of membrane glycoproteins. These changes found in both N- and O-linked oligosaccharides affect mainly β1-6-branched lactosamine antennae which are dramatically increased. Unlike other linkage for lactosamine antennae, the β1-6 linkage allows this antenna to fold back toward the protein backbone where it could affect protein conformation and activity. This review summmarizes our current understanding of the glycosylation changes induced by human T lymphocyte activation and discusses their putative functions in lymphocyte physiology and immune response.
Specialized plasma membrane domains called coated pits are key regulatory sites in glycoprotein biology. There, glycoproteins destined for endocytosis or receptors which are themselves glycoproteins are clustered and processed for internalization. The structural components and the regulatory mechanisms active at coated pits are the subject of intense investigation. Studies with the asialoglycoprotein (ASGP) receptor have elucidated many of these mechanisms, such as a sorting signal responsible for rapid internalization and the intracellular compartments involved in receptor trafficking. Recent data with this receptor suggest that tyrosine kinase activity specifically influences the rate of receptor internalization. A model of glycoprotein endocytosis is thus suggested where, in addition to their role in signal transduction, tyrosine kinases function in the regulation of the early endocytic pathway.
The immunoglobulin is a glycoprotein consisting of heavy and light chains on which the carbohydrate chains are located, normally in the heavy chain constant region. Although immunoglobulin light chains usually lack carbohydrates, some light chains contain carbohydrate chains in their variable region. In this mini review we will discuss the structure, role and modification of carbohydrates on immunoglobutin light chains. We have found an N-glycosylated carbohydrate chain on the light chain-hypervariable region of a human monoclonal antibody which is reactive to lung adenocarcinoma and is produced by a human hybridoma. A carbohydrate chain linked to one of the light chain glycoforms is characterized as hybrid-type, which is rare for any immunoglobulin isotype. To clarify the role of carbohydrates in the light chain variable region, we attempted to modify the glycosylation on this particular light chain. Carbohydrate moiety changes on this light chain produced in concanavalin A-resistant hybridoma clones and the following treatment of these variant light chains with various glycosidases leads to an alteration in the antigen binding activity. To modify the antigen-binding activity of the antibody by altering glycosylation on the light chain, we examined the effects of varying availability of glucose and other monosaccharides in the culture medium. Appropriate N-glycosylation on the light chain, which leads to higher antigenbinding, can be accomplished by modulating monosaccharide availability in the culture medium. Cell clones lacking sensitivity to a glucose level change for light chain glycosylation were screened from the lectin-resistant variants to obtain clones which produce glycoforms reproducibly in various culture environments.