Novel Chemistry to Monitor and Manipulate the Immune System

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This project will develop a chemistry-based approach to monitoring and manipulating the immune system. If successful, it will provide a diagnostic platform of extraordinary utility as well as lead compounds for drugs to inhibit specific immune responses without general immunosuppression. We will employ microarrays comprised of thousands of peptide-like compounds called peptoids and hybridize serum samples to these arrays, resulting in the binding of thousands of proteins and several cell types to the immobilized peptoids. The hybridization pattern of interest will be visualized using an appropriate fluorescently labeled antibody, for example a labeled anti-IgG antibody will "light up" the pattern of binding of all IgG antibodies. Each antibody will evince a different pattern of binding to the array based on the spectrum of affinities of that molecule for the thousands of peptoids on the array. The weighted sum of these binding signatures is expected to provide a "superpattern" that should provide a sensitive readout of the population of circulating antibodies. By comparison of appropriate patients and matched control samples, we should be able to identify features in the superpatterns that are common to the disease of interest, reflecting capture of autoantibodies that are amplified in an autoimmune disease, cancer, a particular infection, etc. The same type of experiment could be done to identify disease state-associated T cells. The most informative peptoids could be used as pseudo biomarkers for diagnosis. Finally, the peptoids identified as good pseudo biomarkers for the disease state will be examined as possible therapeutic agents in various autoimmune conditions, the idea being that these peptoids may capture antibodies or T cells that are not only indicative of the disease, but may be causative as well. This approach holds out the possibility of discovering reagents capable of blocking specific immune responses without global suppression of the immune system.