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Immune system's bare essentials used to speedily detect drug targets
Date:10/31/2010

methods, which rely on sequencing, or identifying every single peptide in the antigen's make-up, one after another. Such sequencing can take months, or even years, to identify possible T cell binding sites.

"The added beauty of our system is that the entire process can be done in the lab, so we do not have to perform tests in people," says Sadegh-Nasseri, who has a patent pending for the new test.

The Johns Hopkins team, including co-lead investigators AeRyon Kim, Ph.D., and Isamu Hartman, Ph.D., also immunologists, based their test on nearly 20 years of the team's previous research into how immune system cells selectively process antigens and the maze of possible protein combinations inside. That cumulative research led them to narrow their search to five essential and well-described proteins involved in antigen processing by immune system cells.

In their latest series of experiments, the team tested a mix of the selected immune system proteins to see if it could accurately detect two already known epitopes, those of the Texas strain of the influenza virus and type II collagen, both widely used experimental antigens. Then, they used the mix to find unknown epitopes for portions of the influenza virus that causes avian flu and for the parasite involved in malaria.

Chief among the epitope-mapping test's chemical components was a protein molecule common to all the body's immune system cells, called HLA-DR. This molecule is one of the most common binding molecules used in the natural immune system's peptide selection process. HLA stands for human leukocyte antigen, and HLA-DR is produced in a gene-dense region of the body's immune system, the major histocompatibility complex.

Other key chemicals in the make-up were HLA-DM, another protein compound that disrupts the binding of HLA-DR molecules to an antigen if the fit is not perfect, and three of the most common enzymes, so-called cathepsins, involved in breaking up
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Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
Source:Eurekalert

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