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
Members

Prof. Dr. Lars Bertram

Full member

University of Lübeck
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA)

Dr. Stefanie Derer

Full member

UKSH Campus Lübeck
Institute of Medical Nutrition Science
RG Molecular Gastroenterology

Prof. Dr. Marc Ehlers

Full member

UKSH Campus Lübeck
Institute of Medical Nutrition Science
Immunology and Glycoanalytics

Dr. Eva Ellinghaus

Full member

Kiel University
Institute of Clinical Molecular Biology
Centre for Molecular Biosciences

Prof. Dr. David Ellinghaus

Full member

Kiel University
Institute of Clinical Molecular Biology
Centre for Molecular Biosciences

Prof. Dr. rer. nat. Andre Franke

Full member

Kiel University
Institute of Clinical Molecular Biology
Genetics & Bioinformatics

Prof. Dr. Sabine Fuchs

Full member

UKSH Campus Kiel
Department of Trauma Surgery
Experimental Orthopaedics and Trauma Surgery

Dr. med. Rainer Günther

Full member

UKSH Campus Kiel
Department of Internal Medicine I

Prof. Dr. med. Guido Heine

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. med. Bimba Franziska Hoyer

Full member

UKSH Campus Kiel
Department of Internal Medicine I
Section Rheumatology

Prof. Dr. rer. nat. Andreas Hutloff

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. Saleh Ibrahim

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Genetics of Inflammatory Diseases

Prof. Dr. rer. biol. hum. Ottmar Janssen

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. med. Dietrich Kabelitz

Full member

UKSH Campus Kiel
Department of Immunology

M.Sc. Sina Kaiser

Associated member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology
AG Prof. Heine

PD Dr. Kathrin Kalies

Full member

University of Lübeck
Institute for Anatomy

Dr. rer. nat. Anika Kasprick

Associated member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
AG Prof. Ludwig

Prof. Dr. Claudia Kemper

Full member

University of Lübeck
Institute for Systemic Inflammation Research

Prof. Dr. Jörg Köhl

Full member

University of Lübeck
Institute for Systemic Inflammation Research

Prof. Dr. rer. nat. Ben Krause-Kyora

Full member

Kiel University
Institute of Clinical Molecular Biology
Ancient DNA Research

Priv.-Doz. Dr. Marcus Lettau

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. Ralf Ludwig

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Model Systems of Inflammatory Skin Diseases

Prof. Dr. Silke Meiners

Full member

Kiel University
Institute of Experimental Medicine
c/o Research Center Borstel - Leibniz Lung Center

Immunology and Cell Biology
Priority Research Area Chronic Lung Diseases

Prof. Dr. med. Franz-Josef Müller

Full member

UKSH Campus Kiel
Department of Psychiatry and Psychotherapy
Center for Integrative Psychiatry gGmbH

Prof. Almut Nebel

Full member

Kiel University
Institute of Clinical Molecular Biology
Longevity Ancient DNA Research

Dr. rer. nat. Christian Peters

Associated member

UKSH Campus Kiel
Department of Immunology
AG Prof. Kabelitz

Prof. Dr. Karina Reiß

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. Gabriela Riemekasten

Full member

UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology

M.Sc. Gabriela Rios Martini

Associated member

UKSH Campus Kiel
Institute of Clinical Molecular Biology
AG Prof. Bacher

Prof. Dr. Jan Rupp

Full member

UKSH Campus Lübeck
Department of Infectious Diseases and Microbiology

Dr. rer. nat. Carina Saggau

Associated member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. rer. nat. Alexander Scheffold

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. med. Stefan Schreiber

Spokesperson

Kiel University
Institute of Clinical Molecular Biology

Prof. Dr. rer. nat. Susanne Sebens

Full member

UKSH Campus Kiel
Institute of Experimental Cancer Research

Dr. oec. troph. Ina Suhrkamp

Associated member

UKSH Campus Kiel
Department of Dermatology, Venereology, and Allergology
AG Prof. Heine

Prof. Dr. Andreas Tholey

Full member

UKSH Campus Kiel
Institute of Experimental Medicine
Systematic Proteomics

M. Sc. Alba Troci

Associated member

Kiel University
Institute of Clinical Molecular Biology
AG Prof. Franke

Prof. Dr. med. Thomas Valerius

Full member

UKSH Campus Kiel
Department of Internal Medicine II
Stem Cells and Immunotherapy

Dr. Artem Vorobyev

Associated member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology

Prof. Dr. Daniela Wesch

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. Detlef Zillikens

Full member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology