To study the interaction of T and B cells that leads to the formation of antibodies in celiac disease, we rely on in vivo (animal) models. We have recently generated a B-cell receptor knock-in mouse strain that is based on the sequence of an anti-TG2 antibody of a celiac disease patient. A T-cell receptor (TCR) transgenic mouse that has T cells that recognizes a gluten epitope (from gamma-gliadin) is available (du Pré et al, 2011). The most immunodominant T-cell responses in celiac disease are however not directed against epitopes in gamma-gliadins, but rather against epitopes in alpha and omega gliadin proteins. We have therefore recently made a TCR transgenic mouse that recognizes the alpha2 gliadin T-cell epitope as well as a TCR transgenic mouse specific for omega2 gliadin T-ell epitope.
Master project: Characterization of new TCR transgenic mice
The master project will aim to characterize an compare the newly generated TCR transgenic mice strains. The student will isolate T cells from peripheral lymphoid organs (spleen and lymph nodes) of mice. Expression of the TCR on T cells will be verified by flow cytometry after staining with antibodies or recombinant gluten-HLA-DQ2 molecules (tetramers). The function of T cells expressing the different T-cell receptors will be compared in T-cell proliferation assay
Methods: In this project the student will gain experience in cellular immunology techniques like isolation of mouse T cells from lymphoid organs, cell culture, flow cytometry, proliferation assays and ELISA.
Workplace: The Sollid group is localized at Rikshospitalet and is a part of the Centre for Immune Regulation (CIR). The MSc student will be integrated with people in the Sollid group working on mouse immunology (senior researcher Jorunn Stamnaes and postdocs Fleur du Pre and Jana Blazevski).
About CIR . The scientific goal of CIR is to identify mechanisms of immune dysregulation that contribute to autoimmune and allergic disease. Three models of autoimmune and allergic disease are studied in detail to identify novel mechanisms amenable to therapeutic intervention. Applying new information, we will develop and implement innovative agents for use in therapy. This work will involve a combination of basic research, research using animal and human disease models which will be carried out by the multidisciplinary Centre. CIR is a collaborative of seven research groups at the University of Oslo/Oslo University Hospital led by Oddmund Bakke, Bjarne Bogen, Frode Jansen, Shuo-Wang Qiao, Ludvig Munthe, Inger Sandlie and Ludvig Sollid. Sollid is center leader and Sandlie deputy leader. The Sollid group was recently selected to be one of five world leading research communities at the University of Oslo (see http://www.uio.no/english/research/news-and-events/news/2015/the-university-of-oslo%E2%80%99s-five-world-leading-resear.html). The Sollid group is actively collaborating with the Jahnsen, Sandlie, Qiao groups at CIR.