Functional analysis of the adhesion receptor CD155 and its ligands

• Applicant: Dr. Günter Bernhardt
• Subject Area: Immunology
• Term: from 2004 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5423572

CD155 represents an adhesion receptor of the immunoglobulin superfamily. Expressed on endothelial or epithelial cells, CD155 contributes to the establishment of adherens junctions by complexing to nectin-3. However, CD155 is also expressed on a variety of hematopoietic cells such as dendritic cells, NK cells and T cells. In the past and present funding period we succeeded to demonstrate roles of CD155 in the immune system and our own results as well as that of others suggest that binding of CD155 to the ligands CD96, CD226 or TIGIT are of primordial importance to accomplish immune relevant tasks. In the coming funding period we wish to focus on the function of CD155 and its ligands in the biological activities of regulatory T cells (Treg) and CD8 T effector cells, a subject that has been neglected in research so far. In our research plans, we will include monoclonal antibodies established in our lab and neutralizing the binding of each of the ligands to CD155. Moreover, mice deficient for CD155, CD226 or TIGIT are available from our own breeding. It is also intended to establish bone marrow chimeric animals providing genetically modified T cells for the experiments. To this end, CD155 deficient bon marrow will be transduced retrovirally to express either wild type CD155 or mutants thereof. This will help elucidating the molecular basis of CD155 functions. Classical in vitro approaches will be combined with in vivo experiments to explore the contribution of CD155 and its ligands in proliferation of CD4 and CD8 T cells as well as the assumed influence on the modulatory capacity of Treg on T cell proliferation and function. We will make use of in vivo models of graft-versus-host-disease (GVHD) and antigen induced arthritis to study the role of CD155 and its ligand in the context of disease. It will also be of interest to explore a putative contribution of this receptor/ligand-system in the generation and function of induced Treg. To specifically address the impact of CD155 and its ligands on CD8 T cell function, we will utilize a diabetes model based on RIP-ova mice and establish a tumour model making use of CD8 OTI cells and the tumour cell line EG7 expressing a surface bound version of ovalbumin. Tumour cells will be included that were engineered to express wild type or mutant CD155 to address the importance and molecular basis of CD155 driven interactions in tumour clearance.

• DFG Programme: Research Grants