The objective of the research proposed is the elucidation, at the molecular level, of the roles cell surface carbohydrates play in the interactions between B and T lymphocytes, between lymphocytes and macrophages, and between natural-killer lymphocytes and their tumor target cells. The research is directed at, 1) the identification of cell surface carbohydrate binding proteins, using modified, iodinated glycoproteins as prbes, 2) the nature of the natural cell surface ligands for these binding proteins, using a combination of enzymatic and chemical labeling techniques in conjunction with a new approach using reverse affinity chromatography and purified binding proteins to isolate these natural ligands, and 3) the potential role of cell surface glycosyltransferases or glycosidases, which have the potential to alter the interactions between the ligands and the carbohydrate binding proteins by addition or removal of sugar residues. These will be studied using a variety of glycoprotein derivatives with specific carbohydrate side chains whose structures may be manipulated using a variety of chemical means, and enzymatically with purified glycosyl transferases and glycosidases. A new approach to the detection of surface glycosidases is described using enzymatically 14C labeled glycoprotein derivatives. The involvement of these three aspects of cell surface carbohydrates in cell interactions will be assessed using two types of cell-cell interactions involving lymphocytes, 1) the interactions between subclasses of lymphocytes, either with themselves or with macrophages, following mitogen (PWM, SpA and Con A) stimulation using 3H thymidine incorporation and Beta 2 microglobulin production to follow transformation, and 2) the interaction of natural killer lymphocytes with turmor target cells, using either FITC labeled cells, or 51Ci labeled target cells.