Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS


MHC CLASS II-OMICS Berichtzusammenfassung

Project ID: 249951
Gefördert unter: FP7-IDEAS-ERC
Land: Netherlands

Final Report Summary - MHC CLASS II-OMICS (Towards understanding and manipulation of MHC class II antigen presentation)

MHC class II molecules are master regulators of immune responses. They are polymorphic and one of the two classes of transplantation antigens. Their aim is to present antigens degraded in the endosomal pathway at the cell surface for consideration by CD4+ T cells that are also named Thelper cells. These CD4+ T cells control many aspects of the immune system after their activation by recognition of defined MHC class II-antigen fragment combinations. As a consequence, various forms of MHC class II are strongest associated to virtually all auto-immune responses.

This defined the goal of the ERC proposal: to define the biology of MHC class II antigen presentation and to translate that in ways to manipulate this process for the control of immune-related diseases.

We have considered the role of each and every protein in the control of MHC class II expression and antigen presentation. This is a long list. By developing a multidimensional screen, we could place these hits in various meaningful clusters and use these clusters to define new biology. This resulted in a number of pathways explaining how proteins control the transport of MHC class II in cells including the dendritic cells that control the immune system. By integrating chemical library screens with siRNA screens, we identified novel target-novel lead combinations that may be applied in the control of MHC class II associated auto-immune diseases. Full clinical application will require more work.
Our work also moved into new and unexplored regions of biology. This resulted in a series of experiments that showed how Salmonella Typhi causes gallbladder cancer. This cancer is frequent in India and Pakistan, unlike in the Western World where Salmonella Typhi infections are rare. In principle, this tumor can be prevented by controlling this infection.

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