Defining disease-associated T and B cell repertoires in chronic inflammatory bowel diseases

Principal Investigator

Prof. Dr. rer. nat.

Associated Doctoral Researcher

Background and current state of research

Chronic inflammatory bowel diseases (IBD), caused by a malfunction of the patients’ immune system towards their environment, are not only still incurable and therefore decreasing the quality of life, but are also an increasing burden for the societies and healthcare systems. Previous research results suggest that the HLA class II region and CD4+ T-cells are of central importance in IBD. Following antigen-dependent clonal activation, expansion and affinity maturation, T and B lymphocytes are primary mediators of chronic inflammation and contribute to the pathogenesis of inflammatory diseases.
Several studies suggest that alterations in the antigen receptor repertoires are involved in Inflammatory Bowel Diseases (IBD) development, although comprehensive studies assessing the full T cell receptor (TCR) and B cell receptor (BCR)/immunoglobulin (Ig) repertoire are missing so far.
IBD is associated with increased numbers of T cells and plasma cells in the intestinal mucosa. Analysis of TCR-β chains revealed a skewed repertoire with reiterative TCR-β chain sequences in intestinal lamina propria and peripheral blood T cells in CD and UC in accordance with antigendependent expansion of T cell clones12. Nevertheless, these analysis did not yet pursue a comprehensive assessment of the immune repertoire diversity.

1. Probert, C. S. et al. Persistent clonal expansions of peripheral blood CD4+ lymphocytes in chronic inflammatory bowel disease.
   J. Immunol. 157, 3183–91 (1996).
2. Probert, C. S. J., Saubermann, L. J., Balk, S. & Blumberg, R. S. Repertoire of the αβ T-cell receptor in the intestine.
    Immunol. Rev. 215, 215–225 (2007).

Our goals

Based on novel technical developments as population and single cells next-generation sequencing approaches for TCR and BCR/Ig analysis, we aim to:

•   define the existence and nature of disease-specific TCR and BCR/Ig repertoires in IBD patients;

•   investigate the degree of overlap between the antigen receptor repertoire in IBD patients and healthy individuals as well as between
    mucosal and systemic compartments;

•   obtain insight into the nature of antigens recognized by IBD-specific immune cell receptors.