Defects in immunoregulatory mechanisms have been associated with several serious disease states, notably, autoimmunity, cancer and immunodeficiencies. Among the latter the acquired immunodeficiency syndrome (AIDS) has become a major threat to public health. The present investigations will examine the cellular and molecular mechanisms underlying various immunodeficiency states and will attempt to develop an experimental basis for potential new therapies to reverse these conditions. Thus it is proposed to complete the biochemical purification and characterization of the previously described, lymphocyte-derived soluble suppressor factor (SSF), an approximately 17 kd polypeptide capable of down-- regulating several different lymphocyte functions in vitro, particularly natural killer cell activity. Preliminary studies have demonstrated that SSF may be a natural lectin which binds to target cells by recognizing specific glycosylated residues. Additional experiments will define the specific mode of action of SSF. A major aim of these studies is the development of methodologies to produce preparative amounts of SSF. Attempts will be made to clone cell lines constitutively producing SSF or, preferably, to isolate and clone its structural gene for the production of recombinant product. The development of a molecular probe for SSF may also permit the examination of SSF gene activation in various clinical conditions. Concomitant production of heteroantisera and monoclonal antibodies to SSF will be used to develop a quantitative immunoassay and an immunoaffinity purification method. The long range goal of this project is the application of these experimental findings in the development of new immunotherapeutic reagents for the treatment of patients with cancer and immunodeficiencies including AIDS.
Showing the most recent 10 out of 20 publications
