Laboratory Test Pinpoints Binding Site for T-Cells

An epitope-mapping laboratory test can, within three weeks, pinpoint the unique binding site--or epitope--from any antigen where immune system T cells can most securely attach and attack invading microorganisms or errant cells.

Identifying the best binding site should speed up cancer vaccine development, lead to new diagnostic tests that detect the first appearance of cancer cells, well before tumors develop, and sort out disorders that are difficult to diagnose, such as Lyme disease.

Scientists at Johns Hopkins School of Medicine (Baltimore, MD, USA) have taken a less-is-more approach to designing effective drug treatments that are precisely tailored to disease-causing pathogens, such as viruses and bacteria, and cancer cells, any of which can trigger the body's immune system defenses.

Knowing exactly where the best antigen-T-cell fit occurs--at sites where peptides bind and are displayed on the surface of antigen-processing immune system cells--is a prerequisite for designing effective and targeted drug therapies, said the scientists.

"Our new, simplified system reproduces what happens in the cells of the immune system when antigens from a pathogen first enter the body and need to be broken down into peptides to become visible to T cells, one of the two immune defender cell types," said immunologist Scheherazade Sadegh-Nasseri, Ph.D., an associate professor of pathology, biophysics, and biophysical chemistry at the Johns Hopkins University School of Medicine. "Once T cells recognize an antigen, they latch on, become activated, and call for other immune system cells to enter the fight," added Prof. Sadegh-Nasseri, the senior study investigator for the team of scientists who developed the new epitope-mapping process.

Prof. Sadegh-Nasseri said that the new lab test takes a fraction of the time involved in current 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.

A report of the new test was published in the online October 31, 2010 issue of Nature Medicine.

Related Links:
Johns Hopkins School of Medicine