This cubic equation may have either two positive roots (and) or no positive roots (no adhesion irrespective of). our comparison with data from Jurkat T cells also points toward mechanisms relating epitope immobility to cell adhesion. == Introduction == When a pathogen elicits a humoral immune response, antibodies are produced that bind to specific epitopes on the surface of the pathogen. Once antibodies have bound to the pathogen, it is labeled as foreign, and various processes can follow that lead to its elimination. One such process, antibody-dependent cell-mediated cytotoxicity (ADCC), involves natural killer (NK) cells binding through their FcRIIIa (CD16a) receptors to IgG antibodies decorating the pathogen (reviewed in[1]). The coupling of an NK cell to a target cell brings parts of the surfaces of the two cells into proximity, within roughly 100. In the region of tight contact where antibodies form bridges between the two cells, both the density of epitopes on the target cell and the density of Fc receptors on the NK cell are locally increased. When the density of Fc receptors in the contact region on the NK cell is sufficiently Fosamprenavir Calcium Salt high, a cellular response is triggered, the end point of which is the release of lytic granules containing perforin and granzymes, whose combined effect results in the killing of the target cell[2][4]. Depending on the nature of the epitope and type of cell, the aggregation of epitopes on the target cell may also trigger cellular responses[5],[6]. Monoclonal antibodies and antibody-like fusion proteins have been developed to take advantage of ADCC. These drugs target naturally occurring proteins that are overexpressed on tumor cells and on populations of cells that drive autoimmune responses[1],[7][10]. Unfortunately, these drugs will also target a subset of healthy cells because the target is a naturally occurring protein. An obvious question, which we address in this paper, is what properties of a drug, the cells that express Fosamprenavir Calcium Salt the target protein, and the NK cells determine a drug’s ability to discriminate between pathogenic and healthy cells? A second question that we consider, that is closely related to the first, is what determines the range of drug concentrations over which a drug will couple target cells to NK cells? These drugs, either in Fosamprenavir Calcium Salt animal models or patients, must compete for Fc receptors on NK cells with endogenous IgG[11]. We therefore also examine how background IgG influences the range of drug concentrations over which adhesion occurs. We previously presented an equilibrium model that describes the coupling via a monoclonal antibody (or an appropriate fusion protein) of identical target cells to a surface expressing mobile Fc receptors[12]. Here, we significantly extend our model to allow for a target cell population with a distribution of surface epitope density. This Fosamprenavir Calcium Salt allows us to analyze experiments where the percentage of bound target cells is determined as a function of the ligand concentration. We also extend the model to admit the possibility of nonspecific adhesion between target cells and the surface. Our extended model also addresses the possibility that some fraction of the target epitopes are Rabbit Polyclonal to PTPRN2 immobile, including cases in which the immobile fraction depends on epitope cross-linking or the size of the contact region. These cases model some potential target cell responses to adhesion. To test predictions of the model, we use an experimental system consisting of a planar bilayer containing mobile FcRIIIb (CD16b) receptors, Jurkat T cells expressing the cell-adhesion molecule CD2, and the drug alefacept that binds the target cell to the bilayer[12]. FcRIIIb differs from FcRIIIa, the receptor on NK cells, in that it lacks a transmembrane region and a.