Molecular Immunology

 / Research

Molecular Immunology

Cytotoxic T and NK cells eliminate infected or transformed cells by the targeted release of effector molecules. Decyphering the molecular regulation of underlying processes is a prerequisite to modulate in order to optimize therapeutical approaches to fight cancer, infections and other immunopathologies.

Group leader:

Ottmar 
Janßen

Prof. Dr. rer. biol. hum.

Group members:

Gerrit 
Hugendieck
Marcus 
Lettau

PD Dr. rer. nat.
Indra 
Sutantio

We are interested in signaling pathways that regulate the activation, effector function and death of NK cells and T lymphocytes. As effector cells of the innate and adaptive immune system, these cell types are in charge of eliminating infected or malignant cells in an immunologically silent fashion. Activation of individual effector cells requires cell-type-specific signals whereas the arsenal of effector proteins widely overlaps. We could recently show that T and NK cells store their live ammunition in distinct storage organelles to mobilize them individually on demand. Presently, we investigate how the targeted release of individual effector proteins might be modulated by differential activation regimen. T and NK cells (as most other cells of the body) also release extracellular vesicles, which may be regarded as a fingerprint of the original cell. We believe that such extracellular vesicles are at least in part derived from the pool of intracellular effector vesicles and are released into the local micromilieu to amplify the immune response by enabling an intracellular communication also at longer distances. To investigate the different phenomena, we employ cell biological, molecular biological and biochemical approaches and methods including cell culture, flow cytometry, imaging flow cytometry, ELISA, Western blotting and proteomics.

  • Lysosoma-related intra- and extracellular effector vesicles in human T and NK cells.
  • Phenotypic and functional characterization of γδ T cells in the context of blinatumomab therapy of acute lymphoblastic leukemias of the B cell lineage

Lettau M, Qian J, Linkermann A, Latreille M, Larose L, Kabelitz D, et al. The adaptor protein Nck interacts with Fas ligand: Guiding the death factor to the cytotoxic immunological synapse. Proc Natl Acad Sci U S A (2006) 103(15):5911–6. doi:10.1073/pnas.0508562103

Lettau M, Kabelitz D, Janssen O. Lysosome-Related Effector Vesicles in T Lymphocytes and NK Cells. Scand J Immunol (2015) 82(3):235–43. doi:10.1111/sji.12337

Lettau M, Armbrust F, Dohmen K, Drews L, Poch T, Dietz M, et al. Mechanistic peculiarities of activation-induced mobilization of cytotoxic effector proteins in human T cells. Int Immunol (2018) 30(5):215–28. doi:10.1093/intimm/dxy007

Lettau M, Dietz M, Dohmen K, Leippe M, Kabelitz D, Janssen O. Granulysin species segregate to different lysosome-related effector vesicles (LREV) and get mobilized by either classical or non-classical degranulation. Mol Immunol (2019) 107:44–53. doi:10.1016/j.molimm.2018.12.031

Lettau M, Dietz M, Vollmers S, Armbrust F, Peters C, Dang TM, et al. Degranulation of human cytotoxic lymphocytes is a major source of proteolytically active soluble CD26/DPP4. Cell Mol Life Sci (2020) 77(4):751–64. doi:10.1007/s00018-019-03207-0.

Prof. Dr. rer. biol. hum. Ottmar Janßen

PD Dr. rer. nat. Marcus Lettau

  • DFG Ja 610/7-3 Lysosome-related intra- and extracellular effector vesicles from human T and NK cells.
  • DJCLS 22R/2019 Phänotypische und funktionelle Charakterisierung von γδ T-Zellen im Rahmen der Blinatumomab-Therapie von akuten lymphoblastischen Leukämien der B-Zell-Reihe
  • Prof. Dr. Dirk Bauerschlag
  • Prof. Dr. Monika Brüggemann, Kiel
  • Dr. Guranda Chitadze, Kiel
  • Dr. Nina Hedemann, Kiel
  • Prof. Dr. Andreas Tholey, Kiel
  • PD Dr. Guido Wabnitz, Heidelberg
  • Prof. Carsten Watzl, Dortmund