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Insight into the immune system

By means of nuclear magnetic resonance on 129Xe atoms, scientists from PTB have managed to spectroscopically demonstrate the bond of a pathogenic germ to a protein which is important for the immune system. This bond is of essential importance for the immune reactions of the body. This work opens up new research fields on the development of magnetic resonance imaging and spectroscopy methodology for immunology.

Xenon atoms permanently move between the solution and the molecular cage (Cage) which is coupled to the HA peptide via a linker (polyethylene glycol and quadripeptide GEEG). This construction can bind to an MHC so that NMR spectroscopy makes it possible to differentiate between three forms: free xenon, xenon in the cage without an MHC bond, and xenon in the cage with an MHC bond.

The immune system continuously checks the operation of somatic cells and organises protection against the permanent att acks of exogenous and toxic substances. In a first step, the invading exogenous antigens (bacteria, viruses, parasites, or their fragments) have to be bound by a certain protein complex designated as "MHC" (major histocompatibility complex class II). This is the precondition for the harmful intruders to be detected by T cells and destroyed during a subsequent immune reaction.

The formation of the complex of antigen and MHC has been investigated at PTB by means of nuclear magnetic resonance measurements on 129Xe atoms. Since xenon, a noble gas, can hardly be responsive to any other bonds, it is bound to the antigen, in the present case a fragment of the influenza virus (haemagglutinin; the fi gure shows HA peptides), by means of a molecular cage and of a so-called linker. Unhindered by its new appendix, the virus fragment then binds to the MHC protein in an aqueous solution. This complex formation can be demonstrated by means of nuclear magnetic resonance. It is possible to observe the binding of antigen to MHC at concentrations as low as 5 µmol/l. By exploiting the exchange process of xenon atoms between the molecular cage and the solution, the complex formation can even be detected at nano molar concentrations – an important requirement for observing the antigen binding by MHC in cell cultures or natural tissues.

This work was successfully carried out in collaboration with the Leibniz-Institut für Molekulare Pharmakologie (FMP) and the Max-Delbrück-Centrum für Molekulare Medizin (MDC) in Berlin. The methodology used is to be still further improved and is to support physicians, e.g., in finding the causes of an autoimmune disease.

Contact at PTB:

Phone: +49-531-592-0