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Sebastian Springer, Professor of Biochemistry and Cell Biology at Jacobs University Bremen, together with scientists from the Royal Holloway University of London, has demonstrated for the first time how the transport of immune reaction key proteins to their reaction site at the cell surface is regulated. The results of the study are published in the current online issue of the Journal of Biological Chemistry (doi:10.1074/jbc.M701721200).
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Oct
18, 2007]
To combat a virus infection, the human immune system needs to identify infected cells. As viruses usually proliferate inside cells, they cannot be detected by antibodies or immunoactive lymphocytes that circulate in the bloodstream. These intracellular viruses are detected by special transport proteins, the so-called MHC (Major Histocompatibility Complex) class I molecules. They bind protein fragments – peptides – and carry them to the cell surface, where the lymphocytes can recognize them as virus components and thereby identify the infected cell, which then is eliminated. Up to now, the question of the transport regulation of MHC class I molecules, especially how they are triggered to move to the cell surface when they bind peptides, has remained mysterious.
Sebastian Springer and his team at Jacobs University, together with Rainer Duden, Professor of Cell Biology and Biochemistry at Royal Holloway University London, have now demonstrated a transport regulation process similar to that of hormones and cell surface receptors: Independent of their receptive status, the MHC class I molecules leave the endoplasmic reticulum (ER), where they are generated inside the cell, in “shipping containers” – the vesicles. They are initially transported to an intermediate “quality check point”, the Golgi apparatus. Peptide-receptive molecules that lack a certain structural firmness are transported back to the ER while peptide-occupied molecules migrate on to the cell surface. The accepted doctrine so far assumed that peptide-receptive MHC class I molecules are not able to leave the ER, which left the control mechanism of their receptive status completely inexplicable.
The researchers used cell cultures of human and hamster lymphocytes for their investigation. They studied the trafficking of peptide-receptive class I molecules in single cells by fluorescence microscopy and assessed their exit rates from the ER using a novel in vitro isolation technique for vesicles.
“The anti-viral immune response appears to be regulated by a mechanism that is very precise and highly efficient. Ultimately our research to understand this mechanism aims at vaccine optimization as well as medical support of the immune system,” comments Jacobs scientist Sebastian Springer on the research results.
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