Autophagy-mediated antigen presentation for CD1d-restricted NKT cell recognition

• Applicant: Dr. Christian Keller
• Subject Area: Immunology
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 221525011

In the proposed research, we aim to investigate whether autophagy regulates natural killer T (NKT) cell responses through delivery of antigens (Ags) to CD1d-loading compartments. Autophagy is a highly conserved lysosomal catabolic pathway during which cell organelles and long-lived proteins are degraded in order to provide nutrients for cell survival. Aside from its involvement in homeostasis, cell death and cellular clearance, autophagy appears to play a crucial role in facilitating antigen presentation via autophagosomes in antigen-presenting cells (APCs). NKT cells represent a T lymphocyte subpopulation sharing functional characteristics with both conventional T cells as well as natural killer cells. NKT cells are believed to be pivotally involved in the mediation between innate and adaptive immune processes by recognizing lipid Ags presented via CD1d molecules. We hypothesize that autophagy facilitates NKT cell responses through transport of lipid Ags to CD1d-loading compartments. To address the aforementioned hypothesis, we will analyze whether autophagosomes colocalize with CD1d-loading compartments in professional APCs during the steady state and following immune activation as well as whether disruption of autophagy in APCs reduces CD1d presentation and NKT cell activation in vitro and in vivo. The experimental set up used to carry out the required analyses will include flow cytometry, human and mouse myeloid cell lines, ELISA, siRNA-mediated knockdown, mice experiments involving conditional knockout mice for disruption of autophagy as well as immunocytochemical co-localization studies via confocal microscopy. The results are expected to further our understanding of the molecular interactions between autophagy-mediated Ag presentation via CD1d molecules and consecutive NKT cell responses. Modulation of CD1d-restricted NKT cell activity might provide new therapeutic options for the treatment and prevention of (auto-) immune-mediated conditions

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Jan Lünemann