TI-2: Integrative Immmunogenetics and Cellular Approaches toward Developing an Antigen-Specific Therapy

Coordinators: P. Bacher (CAU), Andre Franke (CAU), A. Scheffold (CAU), T. Lenz (MPI)

The members of TI-2 want to identify potential triggers of chronic inflammatory bowel disease (IBD). The inflammation is maintained by immune cells so called T cells, which mistakenly target harmless intestinal components, for example parts of the microbiome or food components, and in this way lead to tissue damage. The researchers in TI-2 want to identify novel and patient-specific therapeutic targets and diagnostic opportunities with the aim of selectively switching off the disease-causing T cells.

What does this research area’s work build on?

T cells, which can be activated by intestinal antigens, contribute significantly to IBD pathogenesis, and are thus potential drivers of both, the disease as well as resistance to treatment. T cells recognize antigens, which are presented by HLA molecules on antigen-presenting cells. The scientists in TI-2 have already identified HLA class II susceptibility alleles in IBD patients, which supports the idea of HLA-T cell interactions as potential drivers of disease. However, the specific antigens which are recognized by T cells, the type of T cell responses to different antigens, as well as the patient-specific contribution of individual HLA risk alleles, have not yet been defined.

 

What are the main research objectives?

Based on the genetic and T cell analyses, the research area has developed an integrative research agenda to identify T cell target antigens related to IBD. The goal is to develop new antigen-specific and patient-specific diagnostic approaches and personalized antigen-specific treatment strategies for IBD patients. To this end, the members want to identify potentially disease-causing environmental microbes, antigens, proteins and peptides, and then quantitatively and qualitatively characterize the disease-relevant T cells.

 

What makes this research area special?

The members have developed a new methodology which enables them to identify potential disease-causing T cells and the constituents of the microbiome which they react to, and thus characterize the disease-related changes. Using this, the properties of the pathogenic cells should be precisely identified in TI-2, and then specifically switched off in treatment. In addition, the research area is very interdisciplinary, with researchers from immunology, evolutionary biology, genetic epidemiology and bioinformatics working very closely together.

 

What does the research area contribute to precision medicine in chronic inflammation?

The identification of clinically relevant IBD antigens and specific T cells is the basis for antigen-specific and patient-specific diagnostics and immunotherapy. The correction of the pathogenic adaptive immune response makes it possible to break the vicious cycle of IBD becoming chronic, and thus represents a novel and potentially curative therapeutic approach. If the potential antigen comes from the environment, it could simply be avoided. Relevant antigens from bacteria could possibly be eliminated by specific phage therapy.

 

Cooperation with other research areas in the cluster
  • RTF II: Microbiome analysis, in order to identify possible target antigens, especially within the microbiota
  • RTF III: Epigenetic signatures and modification of pathological T cell responses
  • RTF IV: Cytometry facility: sorting and characterization of disease-relevant T cells
  • RTF VI: Sequencing tools to comprehensively characterize disease-relevant T cells