Research Group Holtappels – Immune control of murine cytomegalovirus infection

Background

The major research topic of our group is the study of the immune control of cytomegalovirus (CMV) infection in mouse models. Control of CMV infection is dominated by CD8 T cells which are able to control the infection, but which are not able to clear the virus from the infected host. Our work aims at understanding this highly balanced virus host relationship under different immunological conditions.

Selected Publications

  1. Holtappels R, Büttner JK, Freitag K, Reddehase MJ, Lemmermann NA. Modulation of cytomegalovirus immune evasion identifies direct antigen presentation as the predominant mode of CD8 T-cell priming during immune reconstitution after hematopoietic cell transplantation. Front Immunol. 2024 Feb 15;15:1355153. doi: 10.3389/fimmu.2024.1355153. PMID: 38426094

  2. Holtappels R, Becker S, Hamdan S, Freitag K, Podlech J, Lemmermann NA, Reddehase MJ. Immunotherapy of cytomegalovirus infection by low-dose adoptive transfer of antiviral CD8 T cells relies on substantial post-transfer expansion of central memory cells but not effector-memory cells. PLoS Pathog. 2023 Nov 16;19(11):e1011643. doi: 10.1371/journal.ppat.1011643. PMID: 37972198

  3. Hamdan S, Reddehase MJ, Holtappels R. Cytomegalovirus immune evasion sets the functional avidity threshold for protection by CD8 T cells. Med Microbiol Immunol. 2023 Apr;212(2):153-163. doi: 10.1007/s00430-022-00733-w. PMID: 35364731

  4. Freitag K, Hamdan S, Reddehase MJ, Holtappels R. Immunodominant cytomegalovirus epitopes suppress subdominant epitopes in the generation of high-avidity CD8 T cells. Pathogens. 2021 Jul 29;10(8):956. doi: 10.3390/pathogens10080956. PMID: 34451420

  5. Holtappels R, Schader SI, Oettel O, Podlech J, Seckert CK, Reddehase MJ, Lemmermann NAW. Insufficient antigen presentation due to viral immune evasion explains lethal cytomegalovirus organ disease after allogeneic hematopoietic cell transplantation. Front Cell Infect Microbiol. 2020 Apr 15;10:157. doi: 10.3389/fcimb.2020.00157. PMID: 32351904

  6. Reuter S, Lemmermann NAW, Maxeiner J, Podlech J, Beckert H, Freitag K, Teschner D, Ries F, Taube C, Buhl R, Reddehase MJ, Holtappels R. Coincident airway exposure to low-potency allergen and cytomegalovirus sensitizes for allergic airway disease by viral activation of migratory dendritic cells. PLoS Pathog. 2019 Mar 7;15(3):e1007595. doi: 10.1371/journal.ppat.1007595. PMID: 30845208

  7. Chopra M, Biehl M, Steinfatt T, Brandl A, Kums J, Amich J, Vaeth M, Kuen J, Holtappels R, Podlech J, Mottok A, Kraus S, Jordán-Garrote AL, Bäuerlein CA, Brede C, Ribechini E, Fick A, Seher A, Polz J, Ottmüller KJ, Baker J, Nishikii H, Ritz M, Mattenheimer K, Schwinn S, Winter T, Schäfer V, Krappmann S, Einsele H, Müller TD, Reddehase MJ, Lutz MB, Männel DN, Berberich-Siebelt F, Wajant H, Beilhack A. Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion. J Exp Med. 2016 Aug 22;213(9):1881-900. doi: 10.1084/jem.20151563.  PMID: 27526711

  8. Nauerth M, Weißbrich B, Knall R, Franz T, Dössinger G, Bet J, Paszkiewicz PJ, Pfeifer L, Bunse M, Uckert W, Holtappels R, Gillert-Marien D, Neuenhahn M, Krackhardt A, Reddehase MJ, Riddell SR, Busch DH. TCR-ligand koff rate correlates with the protective capacity of antigen-specific CD8+ T cells for adoptive transfer. Sci Transl Med. 2013 Jul 3;5(192):192ra87. doi: 10.1126/scitranslmed.3005958. PMID: 23825303

  9. Ebert S, Podlech J, Gillert-Marien D, Gergely KM, Büttner JK, Fink A, Freitag K, Thomas D, Reddehase MJ, Holtappels R. Parameters determining the efficacy of adoptive CD8 T-cell therapy of cytomegalovirus infection. Med Microbiol Immunol. 2012 Nov;201(4):527-39. doi: 10.1007/s00430-012-0258-x. PMID: 22972232

  10. Holtappels R, Thomas D, Reddehase MJ. The efficacy of antigen processing is critical for protection against cytomegalovirus disease in the presence of viral immune evasion proteins. J Virol. 2009 Sep;83(18):9611-5. doi: 10.1128/JVI.00936-09. PMID: 19553308

  11. Holtappels R, Podlech J, Pahl-Seibert MF, Jülch M, Thomas D, Simon CO, Wagner M, Reddehase MJ. Cytomegalovirus misleads its host by priming of CD8 T cells specific for an epitope not presented in infected tissues. J Exp Med. 2004 Jan 5;199(1):131-6. doi: 10.1084/jem.20031582. PMID: 14699084

Other publications by Prof. Dr. Rafaela Holtappels

Members

Prof. Dr. Rafaela Holtappels

Prof. Dr. Rafaela Holtappels

Principal Investigator

Kirsten Freitag

Kirsten Freitag

Collaboration partner

 

Internal (University Medical Center Mainz, Germany)

External