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Cytomegalovirus memory inflation and immune protection

  • Luka Cicin-SainEmail author
Review
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Abstract

Cytomegalovirus (CMV) infection induces powerful and sustained T-cell responses against a few selected immunodominant antigenic epitopes. This immune response was named memory inflation, because it does not contract in the long term, and may even expand over months and years of virus latency. It is by now understood that memory inflation does not occur at the expense of the naïve T-cell pool, but rather as a competitive selection process within the effector pool, where viral antigens with higher avidity of TCR binding and with earlier expression patterns outcompete those that are expressed later and bind TCRs less efficiently. It is also understood that inflationary epitopes require processing by the constitutive proteasome in non-hematopoietic cells, and this likely implies that memory inflation is fuelled by direct low-level antigenic expression in latently infected cells. This review proposes that these conditions make inflationary epitopes the optimal candidates for adoptive immunotherapy of CMV disease in the immunocompromised host. At present, functional target CMV epitopes have been defined only for the most common HLA haplotypes. Mapping the uncharacterized inflationary epitopes in less frequent HLAs may, thus, be a strategy for the identification of optimal immunotherapeutic targets in patients with uncommon haplotypes.

Keywords

Cytomegalovirus Memory inflation CD8 T cell Proteasome Constitutive proteasome Immunoproteasome Immune protection 

Notes

Acknowledgments

I gratefully acknowledge Iryna Dekhtiarenko for her contribution to the development of the project and data shown in Fig. 2. Furthermore, this project was supported by the Helmholtz Association through the Helmholtz-EU Partnership consortium MCMVaccine, the German Scientific Foundation through the project CRC900, project B2 and the Excellence cluster RESIST, as well as the German Ministry of Education and Science through DZIF funding.

Compliance with ethical standards

Conflict of interest

The authors declare they have no conflict of interest.

Human and animal rights

Data shown in this article were published previously, with the exception of Fig. 2, which was an in vitro study of murine cell lines. CTLs used in the experiment were generated from primary T cells acquired from mice in accordance with institutional and state guidelines and approved as an animal protocol under the running number 33.19-42502-05-10A039 by the Lower Saxony Office for Consumer Protection. No clinical data are shown and no human-derived biological samples were used in this study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Vaccinology and Applied MicrobiologyHelmholtz Centre for Infection Research (HZI)BraunschweigGermany
  2. 2.Cluster of Excellence RESIST (EXC 2155)Hannover Medical School (MHH)HannoverGermany
  3. 3.Centre for Individualised Infection Medicine (CIIM), A Joint Venture of HZI and MHHBraunschweigGermany
  4. 4.German Centre for Infection Research (DZIF)BraunschweigGermany

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