Subdominant CD8 T-cell epitopes account for protection against cytomegalovirus independent of immunodomination

被引：71

作者：

Holtappels, Rafaela ^{[1
]}

Simon, Christian O. ^{[1
]}

Munks, Michael W. ^{[2
]}

Thomas, Doris ^{[1
]}

Deegen, Petra ^{[1
]}

Kuehnapfel, Birgit ^{[1
]}

Daeubner, Torsten ^{[1
]}

Emde, Simone F. ^{[1
]}

Podlech, Juergen ^{[1
]}

Grzimek, Natascha K. A. ^{[1
]}

Oehrlein-Karpi, Silke A. ^{[1
]}

Hill, Ann B. ^{[2
]}

Reddehase, Matthias J. ^{[1
]}

机构：

[1] Johannes Gutenberg Univ Mainz, Inst Virol, D-55131 Mainz, Germany

[2] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA

来源：

JOURNAL OF VIROLOGY | 2008年 / 82卷 / 12期

关键词：

D O I：

10.1128/JVI.00155-08

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Cytomegalovirus (CW) infection continues to be a complication in recipients of hematopoietic stem cell transplantation (HSCT). Preexisting donor immunity is recognized as a favorable prognostic factor for the reconstitution of protective antiviral immunity mediated primarily by CD8 T cells. Furthermore, adoptive transfer of CMV-specific memory CD8 T (CD8-T-M) cells is a therapeutic option for preventing CMV disease in HSCT recipients. Given the different CMV infection histories of donor and recipient, a problem may arise from an antigenic mismatch between the CMV variant that has primed donor immunity and the CMV variant acquired by the recipient. Here, we have used the BALB/c mouse model of CMV infection in the immunocompromised host to evaluate the importance of donor-recipient CMV matching in immundominant epitopes (IDEs). For this, we generated the marine CMV (mCMV) recombinant virus mCMV-Delta IDE, in which the two memory repertoire IDEs, the IE1-derived peptide 168-YPHFMPTNL-176 presented by the major histocompatibility complex class I (MHC-I) molecule L-d and the m164-derived peptide 257-AGPPRYSRI-265 presented by the MHC-I molecule D-d, are both functionally deleted. Upon adoptive transfer, polyclonal donor CD8-T-M cells primed by mCMV-Delta IDE and the corresponding revertant virus mCMV-rev Delta IDE controlled infection of immunocompromised recipients with comparable efficacy and regardless of whether or not IDEs were presented in the recipients. Importantly, CD8-T-M cells primed under conditions of immunodomination by IDEs protected recipients in which IDEs were absent. This shows that protection does not depend on compensatory expansion of non-IDE-specific CD8-T-M cells liberated from immunodomination by the deletion of IDEs. We conclude that protection is, rather, based on the collective antiviral potential of non-IDEs independent of the presence or absence of IDE-mediated immunodomination.

引用

页码：5781 / 5796

页数：16

共 69 条

[1] Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy [J].