Inflammatory bowel diseases (IBD) are thought to result from an aberrant immune reaction against intestinal microbes. This immune reaction is initiated by antigen presenting cells in the bowel wall like macrophages and dendritic cells, which take up luminal antigens and present it on HLA-II molecules to CD4+ T cells in the lamina propria. HLA class II susceptibility alleles have been identified in IBD patients, which supports the idea of HLA-T cell interactions as potential disease drivers. However, the specific disease-driving antigens recognized by T cells and the type of T cell response against different antigens are not yet defined.
Using novel technologies to identify peptides presented on HLA-II alleles and to detect and characterize antigen-specific CD4+ T cells, the aims of this project is to 1) identify potential disease-causing and protective peptides presented on the HLA-II molecules of patients with IBD and 2) to test their immunogenicity and characterize the CD4+ T cell response induced by certain candidate microbial peptides..
The detailed characterization of T cells specific for intestinally presented peptides and their host microbes is a unique approach to identify disease-relevant targets and cellular players in IBD. In the long run, this project will help to identify relevant antigens in the pathogenesis of IBD, which may be used for the development of targeted immune therapies.