Visual Universitätsmedizin Mainz

Immunobiology of Natural Killer (NK) cells

Current Research

 

Natural killer (NK) cells of the innate immune system play an important role for immunosurveillance of infections and cancer. NK cells are activated by target cells with low or absent expression of MHC class I (‘missing-self’) and/or a stress-induced expression of ligands for activating NK cell receptors (‘induced-self’). Consequently, the activation state of NK cells is governed by a predominance of signals from either inhibitory or activating receptors. In humans, major activating receptors include the natural cytotoxicity receptors (NCRs) NKp30, NKp44 and NKp46, whose few cellular ligands identified so far remain poorly characterized on the molecular level, and NKG2D, recognizing a variety of well-defined ligands (MICA, MICB, and several ULBPs). The importance of these activating receptors is underscored by the fact that their surface density correlates with the degree of NK cell cytotoxicity. However, pathogens and malignantly transformed cells have developed sophisticated strategies to disable NK cell-dependent immunosurveillance.

 

Fig. 1: A natural killer cell (NK cell, yellow) of the immune system attacking a cancer cell (red). (Photo courtesy of Prof. Dr. Rupert Handgretinger; with permission of ‘eye of science’ (http://www.eyeofscience.de)).

 

 

The focus of the Koch laboratory is to understand the molecular details of ligand recognition by major activating receptors of NK cells and to elucidate and overcome related tumor immune escape strategies in order to improve the efficacy of cellular cancer therapies. These studies include the investigation of the cellular crosstalk between NK cells with other immune cells and functional consequences.

 

 

 

Lab Members

Prof. Dr. rer. nat. Koch
Prof. Dr. rer. nat. Joachim Koch
Function: Principal Investigator

17-9336
17-9234
joachim.koch@uni-mainz.de

Platzhalterbild
Stefanie Memmer
Function: Ph.D. Student

17-9336
17-9234
memmer@uni-mainz.de

Platzhalterbild
Dr. rer. nat. Sandra Weil
Function: Postdoc

17-9336
17-9234

Publications

Peer-reviewed:

Memmer Stefanie, Weil Sandra, Beyer Steffen, Zoeller Tobias, Peters Eike, Hartmann Jessica, Steinle Alexander, Koch Joachim (2016). The Stalk Domain of NKp30 Contributes to Ligand Binding and Signaling of a Preassembled NKp30-CD3 Complex. JOURNAL OF BIOLOGICAL CHEMISTRY. ; 291(49): 25427-25438 

Kloess, S., Chambron, N., Gardlowski, T., Weil, S., Koch, J., Esser, R., Pogge-von-Strandmann, E., Morgan, M. A., Arseniev, L., Seitz, O., and Koehl, U. (2015) Cetuximab reconstitutes proinflammatory cytokine secretions and tumour-infiltrating capabilities of sMICA-inhibited NK cells in HNSCC tumour spheroids. Frontiers Immunol., 6, article 543

Giannattasio, A., Weil, Kloess, S., Ansari, N., Stelzer, E. H. K., Cerwenka, A., Steinle, A. Koehl, U. and Koch, J. (2015) Cytotoxicity and infiltration of human NK cells in in vivo-like tumor spheroids. BMC Cancer, 15, 351-363

Kuvardina, O. N., Herglotz, J., Kolodziej, J., Kohrs, N., Herkt, S., Wojcik, B., Oellerich, T., Corso, J., Behrens, K., Kumar, A., Hussong, H., Urlaub, H., Koch, J., Serve, H., Bönig, H., Stocking, C., Rieger, M . A., and Lausen, J. (2015) RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation. Blood, 125, 3570-3579

Kloess, S., Chambron, N., Gardlowski, T., Arseniev, L., Koch, J., Esser, R., Glienke, W., Seitz, O., and Koehl, U. (2015) High levels of tumour markers and altered cytokine profiles in HNSCC patients: Induction of impaired functionality of both ex-vivo activated patient-derived and healthy donor NK cells. Oncoimmunology, e1055993

Hinz, A., Jedamzick, J., Herbring, V., Fischbach, H., Hartmann, J., Parcej, D., Koch, J., and Tampé, R. (2014) Assembly and function of the MHC I peptide-loading complex are conserved across higher vertebrates. J. Biol. Chem. 289, 33109-33117

Langers, I., Renoux, V., Reschner, A., Touzé, A., Coursaget, P., Boniver, J., Koch, J., Delvenne, P., and Jacobs, N. (2014) Natural killer and dendritic cells collaborate in the immune response induced by the vaccine against uterine cervical cancer. Eur. J. Immunol., 44, 3585-3595

Trott, M., Weiss, S., Antoni, S., Koch, J., von Briesen, H., Hust, M., and Dietrich, U. (2014) Functional characterization of two scFv-Fc antibodies from an HIV controller selected on soluble HIV-1 Env complexes: A neutralizing V3- and a trimer-specific gp41 antibody. PLoS One, DOI: 10.1371/journal.pone.0097478

Herrmann, J., Berberich, H., Hartmann, J., Beyer, S., Davies, K., and Koch, J. (2014) Homo-oligomerization of the activating natural killer cell receptor NKp30 ectodomain increases its binding affinity for cellular ligands. J. Biol. Chem., 289, 765-777

Binici, J. and Koch, J. (2014) BAG-6, a jack of all trades in health and disease. Cell. Mol. Life. Sci. 71, 1829-1837

Müller, N., Hartmann, C., Genßler, S., Koch, J., Kinner, A., Grez, M. and Wels, W.S. (2014) A novel bispecific transmembrane antibody simultaneously targeting intra- and extracellular epitopes of the epidermal growth factor receptor. Int. J. Cancer. 134, 2547-2559

Binici, J., Hartmann, J., Herrmann, J., Schreiber, C., Beyer, S., Güler, G., Vogel, V., Tumulka, F., Abele, R., Mäntele, W., and Koch, J. (2013) A soluble fragment of the tumor antigen BAG-6 is essential and sufficient for inhibition of NKp30-dependent NK cell cytotoxicity. J. Biol. Chem. 288, 34295–34303

Ullrich, E., Koch, J., Cerwenka, A., and Steinle, A. (2013) New prospects on the NKG2D/NKG2D-ligand system for oncology. Oncoimmunology 2:10, e26097

Koch, J.*, Steinle, A., Watzl, C., and Mandelboim, O. (2013) Activating natural cytotoxicity receptors of NK cells in cancer and infection. Trends Immunol., 34, 182-191 (*corresponding author, Cover Illustration)

Grada, Z., Hegde, M., Byrd, T., Shaffer, D. R., Ghazi, A., Brawley, V. S., Corder, A., Schönfeld, K., Koch, J., Dotti, G., Heslop, H. E., Gottschalk, S., Wels, W. S., Baker, M. L., and Ahmed, N. (2013) TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer Immunotherapy. Mol. Ther.-Nucleic Acids, 2, e105

Dietrich, U., Dürr, R., and Koch, J. (2013) Peptides as drugs: From screening to application. Curr. Pharm. Biotechnol. 14, 501-512

Zhou, M., Meyer, T., Koch, S., Koch, J., Briesen, H., Benito, J. M., Soriano, V., Haberl, A., Bickel, M., Dübel, S., Hust, M., and Dietrich, U. (2013) Identification of an epitope in the membrane proximal external region of gp41 targeted by neutralizing antibodies in plasma from an elite controller using an Env-tailored phage display library. Eur. J. Immunol., 43, 499-509

Hermes, M., Weil, S., Groth, A., Dressel, R., Koch, J., and Walter, L. (2012) Characterization of mouse monoclonal antibodies against rhesus macaque killer immunoglobulin-like receptors KIR3D. Immunogenetics, 64, 845-848

Hartmann, J., Tran T.-V., Kaudeer J., Oberle, K., Herrmann, J., Quagliano, I., Abel, T., Cohnen, A., Gatterdam, V., Jacobs, A., Wollscheid, B., Tampé, R., Watzl, C., Diefenbach, A., and Koch, J. (2012) The stalk domain and the glycosylation status of the activating natural killer cell receptor NKp30 are important for ligand binding. J. Biol. Chem., 287, 31527-31539

Tscheliessnig, R., Zörnig, M., Herzig, E. M., Lückerath, K., Altrichter, J., Kemter, K., Paunel-Görgülü, A., Lögters, T., Windolf, J., Pabisch, S., Cinatl, J., Rabenau, H. F., Jungbauer, A., Müller-Buschbaum, P., Scholz, M. and Koch, J. (2012) Nano-coating protects biofunctional materials. Materials Today, 15, 394-404

Koch, J. (2011) SPOT peptide arrays to study biological interfaces at the molecular level. Mini. Rev. Organ. Chem., 8, 111-113

Groth, A., Klöss, S., Pogge von Strandmann, E., Köhl, U., and Koch, J. (2011) Mechanisms of tumor and viral immune escape from natural killer cell-mediated surveillance. J. Innate Immun., 3, 344-354

Funke, J., Dürr, R., Dietrich, U., and Koch, J. (2011) Natural killer cells in HIV-1 infection: A double-edged sword. AIDS Rev., 13, 67-76

SPOTlight on peptide arrays on solid supports – Applications and perspectives. (2011) Guest edited volume by Koch, J., Mini. Rev. Organ. Chem., 8, 110-177

Wycisk, A. I., Lin, J., Loch, S., Hobohm, K., Funke, J., Wieneke, R., Koch, J., Skach, W. R., Mayerhofer, P. U. and Tampé, R. (2011) Epstein-Barr viral BNLF2a hijacks the tail-anchored protein insertion machinery to block antigen processing by the TAP complex. J. Biol. Chem., 286, 41402-41412

Verweij, M. C., Lipińska, A. D., Koppers-Lalic, D., Quinten, E., Funke, J., van Leeuwen, H. C., Bieńkowska-Szewczyk, K., Koch, J., Ressing, M. E., and Wiertz, E. J. H. J. (2011) Structural and functional analysis of the TAP-inhibiting UL49.5 proteins of varicelloviruses. Mol. Immunol., 48, 2038-2051

Kloess, S., Huenecke, S., Piechulek, D., Esser, R., Koch, J., Brehm, C., Soerensen, J.,  Gardlowski, T., Brinkmann, A., Bader, P., Passweg, J., Klingebiel, T., Schwabe, D., and Koehl, U. (2010) Soluble MICA molecules inhibit NKG2D-dependent cytotoxicity of allogeneic NK cells in children with neuroblastoma after haploidentical SCT. Eur. J. Immunol., 40, 3255-3267

Dervillez, X.*, Klaukien, V.*, Dürr, R.*, Koch, J., Kreutz, A., Haarmann, T., Stoll, M., Lee, D., Carlomagno, T., Schnierle, B., Möbius, K., Königs, C., Griesinger, C., and Dietrich, U. (2010) Peptide ligands selected with CD4-induced epitopes on native dualtropic HIV-1 envelope proteins mimic extracellular coreceptor domains and bind to HIV-1 gp120 independently of coreceptor usage. J. Virol., 84, 10131–10138 (*equal contribution)

Hartmann, C., Müller, N., Blaukat, A., Koch, J., Benhar, I., and Wels, W. S. (2010) Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response. Oncogene, 29, 4517-4527

Baldauf, C., Schrodt, S., Herget, M. Koch, J., and Tampé, R. (2010) Single residue within the antigen translocation complex TAP controls the epitope repertoire by stabilizing a receptive conformation. Proc. Natl. Acad. Sci. U. S. A., 107, 9135-9140

Wichmann, C., Becker, Y., Chen-Wichmann, L., Vogel, V., Vojtkova, A., Herglotz, J., Moore, S., Koch, J., Lausen, J., Mäntele, W., Gohlke, H., and Grez, M. (2010) Dimer-tetramer transition controls RUNX1/ETO leukemogenic activity. Blood, 116, 603-613

Falk, S., Ravaud, S., Koch, J., and Sinning, I. (2010) The membrane insertase Alb3 recruits cpSRP43 and ribosomes to the thylakoid membrane. J. Biol. Chem., 285, 5954-5962

Brandt, O., Dietrich, U., and Koch, J. (2009) Solid-supported peptide arrays in the investigation of protein-protein and protein-nucleic acid interactions. Curr. Chem. Biol., 3, 171-179

Ott, V., Koch, J., Späte, K., Morbach, S., and Krämer, R. (2008) Regulatory properties and interaction of the C- and N-terminal domains of BetP, an osmoregulated betaine transporter from Corynebacterium glutamicum. Biochemistry, 47, 12208-1221

Verweij, M. C., Koppers-Lalic, D., Loch, S., Klauschies, F., de la Salle, H., Quinten, E., Lehner, P. J., Mulder, A., Knittler, M. R., Tampé, R., Koch, J., Ressing, M. E., and Wiertz, E. J. H. J. (2008) The varicellovirus UL49.5 protein blocks Transporter Associated with Antigen Processing (TAP) by inhibiting essential conformational transitions in the 6 + 6 transmembrane TAP core complex. J. Immunol., 181, 4894-4907

Radzimanowski, J., Ravaud, S., Schlesinger, S., Koch, J., Beyreuther, K., Sinning, I., Wild, K. (2008) Crystal structure of the human FE65-PTB1 domain. J. Biol. Chem. 283, 23113-23120

Koppers-Lalic, D., Verweij, M. C., Lipińska, A. D., Wang, Y., Quinten, E., Reits, E. A., Koch, J., Loch, S., Rezende, M. M., Daus, F., Bieńkowska-Szewczyk, K., Osterrieder, N., Mettenleiter, T. C., Heemskerk M. H., Tampé, R., Neefjes, J. J., Chowdhury, S. I., Ressing, M. E., Rijsewijk, F. A., Wiertz, E. J. (2008) Varicellovirus UL49.5 proteins differentially affect the function of the Transporter Associated with Antigen Processing, TAP. PLoS Pathog., 4, e1000080

Loch, S., Klauschies, F., Schölz, C., Verweij, E., Wiertz, E. J. H. J., Koch, J.*, and Tampé, R.* (2008) Signaling of a varicelloviral factor across the ER membrane induces destruction of the peptide-loading complex and immune evasion. J. Biol. Chem., 283, 13428-13436 (* shared corresponding authorship)

Dietz, J.*, Koch, J.*, Kaur, A., Raja, C., Stein, S., Grez, M., Pustowka, A., Mensch, S., Ferner, J., Möller, L., Bannert, N., Tampé, R., Divita, G., Mély, Y., Schwalbe, H., and Dietrich, U. (2008) Inhibition of HIV-1 by a peptide ligand of the genomic RNA packaging signal Ψ. ChemMedChem, 3, 749-755 (* both authors contributed equally)

Plewnia, G., Schulze, K., Hunte, C., Tampé, R., and Koch, J. (2007) Modulation of the antigenic peptide transporter TAP by recombinant antibodies binding to the last five residues of TAP1. J. Mol. Biol. 369, 95-107

van Hall, T., Laban, S., Koppers-Lalic, D., Koch, J., Precup, C., Asmawidjaja, P., Offringa, R., and Wiertz, E. J. H. J. (2007) The varicellovirus-encoded TAP-inhibitor UL49.5 regulates the presentation of CTL epitopes by Qa-1b. J. Immunol. 178, 657-662

Koch, J.* and Tampé, R.* (2006) The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation. Cell. Mol. Life. Sci. 63, 653-662. (* shared corresponding authorship) Cover Illustration

Koch, J.*, Guntrum, R., and Tampé, R. (2006) The first N-terminal transmembrane helix of each subunit of the antigenic peptide transporter TAP is essential for independent tapasin binding. FEBS Lett. 580, 4091-4096 (* corresponding author);

Ernst, R., Koch, J., Horn, C., Tampé, R., and Schmitt, L. (2006). Engineering ATPase activity in the isolated ABC-cassette of human TAP1. J. Biol. Chem. 281, 27471-27480

Aisenbrey, C., Sizun, C., Koch, J., Herget, M., Abele, R., Bechinger, B., and Tampé, R. (2006) Structure and dynamics of membrane-associated ICP47, a viral inhibitor of the MHC I antigen processing machinery. J. Biol. Chem. 281, 30365-30372

van der Sluis, E. O., Nouwen, N., Koch, J., de Keyzer, J., van der Does, C., Tampé, R., and Driessen, A. J. M. (2006) Identification of two interaction sites in SecY that are important for the functional interaction with SecA. J. Mol. Biol. 361 839-849

Schrodt, S., Koch, J., and Tampé, R. (2006) Membrane topology of the transporter associated with antigen processing (TAP1) within an assembled functional peptide-loading complex. J. Biol. Chem. 281, 6455-6462

Koppers-Lalic, D., Reits, E. A. J., Ressing, M. E., Lipinska, A. D., Abele, R., Koch, J., Rezende, M. M., Admiraal, P., van Leeuwen, D., Bienkowska-Szewczyk, K., Mettenleiter, T. C., Rijsewijk, F. A. M., Tampé, R., Neefjes, J., and Wiertz, E. J. H. J. (2005) Varicelloviruses avoid T cell recognition by UL49.5-mediated inactivation of the transporter associated with antigen processing. Proc. Natl. Acad. Sci. U. S. A. 102, 5144-5149

Koch, J., Guntrum, R., and Tampé, R. (2005) Exploring the minimal functional unit of the transporter associated with antigen processing (TAP). FEBS Lett. 579, 4413–4416

Koch, J., Guntrum, R., Heintke, S., and Tampé, R. (2004) Functional dissection of the transmembrane domains of the transporter associated with antigen processing (TAP). J. Biol. Chem. 279, 10142-10147

Liang, M., Mahler, M., Koch, J., Ji, Y., Li, D., Schmaljohn, C., and Bautz E. K. (2003) Generation of an HFRS patient-derived neutralizing recombinant antibody to Hantaan virus G1 protein and definition of the neutralizing domain. J. Med. Virol. 69, 99-107

Usener, D., Schadendorf, D., Koch, J., Dübel, S., and Eichmüller, S. (2003) cTAGE: A cutaneous T-cell lymphoma associated antigen family with tumor-specific splicing. J. Invest. Dermatol. 121, 198-206

Koch, J.*, Liang, M., Queitsch, I., and Bautz, E. K. F. (2003) Human recombinant neutralizing antibodies against Hantaan virus G2 protein. Virology 308, 64-73. (* corresponding author)

Heintke, S., Chen, M., Ritz, U., Lankat-Buttgereit, B., Koch, J., Abele, R., Seliger, B., and Tampé, R. (2003) Functional cysteine-less subunits of the transporter associated with antigen processing (TAP1 and TAP2) by de novo gene assembly. FEBS Lett. 533, 42-46

Costagliola, S., Panneels, V., Bonomi, M., Koch, J., Many, M. C., Smits, G., and Vassart, G. (2002) Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors. EMBO J. 21, 504-513

Yip, Y. L., Smith, G., Koch, J., Dübel, S., and Ward, R. L. (2001) Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-erbb-2 monoclonal antibodies: implications for vaccine design. J. Immunol. 166, 5271-5278

Groves, M. R., Mant, A., Kuhn, A., Koch, J., Dübel, S., Robinson, C., and Sinning ,I. J. (2001) Functional characterization of recombinant chloroplast signal recognition particle. J. Biol. Chem. 276, 27778-27786

Rondot, S.*, Koch, J.*, Breitling, F., and Dübel, S. (2001) A helperphage to improve single chain antibody presentation in phage display. Nat. Biotechnol. 19, 75-78. (* both authors contributed equally)

Koch, J., Breitling, F., and Dübel, S. (2000) Rapid Titration of filamentous Bacteriophage (M13) on nitrocellulose membranes. BioTechniques 29, 1196-1202

Moghaddam, A., Koch, J., Annis, B., and Wang, F. (1998) Infection of human B lymphocytes with lymphocryptoviruses related to Epstein-Barr virus. J. Virol. 72, 3205-3212

 

Other publications:

Koch, J. (2011) Schlauer als die Krebszellen – Biochemiker unterstützen die Arbeit natürlicher Killerzellen. Forschung Frankfurt

Koch, J. (2011) Ökosystem statt Nutzwald. Forschung Frankfurt

Schutkowski, M., Thiele, A., and Koch, J. (2009) Solid-supported peptide arrays in the identification of peptide ligands. Peptides as Drugs – Discovery and Development, ed.: Groner, B., Wiley-VCH, Heidelberg

Bräuning, R., Mahler, M., Hügle-Dörr, B., Blüthner, M., Koch, J., and Petersen, G. (2002) Protein-protein interactions - potential and pitfalls. In: Peptide arrays on membrane supports, ed.: Koch, J., and Mahler, M., Springer, Heidelberg.

Blüthner, M., Koch, J., and Mahler, M. (2002) Mutational analysis and structure predictions. In: Peptide arrays on membrane supports, ed.: Koch, J., and Mahler, M., Springer, Heidelberg.

Mahler, M., Blüthner, M., and Koch, J. (2002) Affinity purification and competition assays using solidphase oligopeptides. In: Peptide arrays on membrane supports, ed.: Koch, J., and Mahler, M., Springer, Heidelberg.

Koch, J., Mahler, M., and Blüthner, M. (2002) Epitope mapping of antibodies with solidphase oligopeptides. In: Peptide arrays on membrane supports, ed.: Koch, J., and Mahler, M., Springer, Heidelberg.

Koch, J., Mahler, M., Blüthner, M., and Dübel, S. (2002) Analysis of protein interactions with peptides synthesized on membranes. In: Protein-protein interactions: A molecular cloning manual, ed.: Golemis, E., Cold Spring Harbor Laboratory Press, New York.

Koch, J., and Mahler, M., eds. (2002) Peptide arrays on membrane supports, Springer, Heidelberg.

Koch, J., and Dübel, S. (2001) Generation of antibody libraries from human donors. In: Antibody engineering, ed: Kontermann, R., and Dübel, S., Springer, Heidelberg.

 

 

 

Funding