Clonotype analysis of cytomegalovirus-specific cytotoxic T lymphocytes

Nina Babel, Gordon Brestrich, Lukasz Gondek, Arne Sattler, Marcin W. Wlodarski, Nina Poliak, Nicole Bethke, Andreas Thiel, Markus H. Hammer, Petra Reinke, Jaroslaw P. Maciejewski

Research output: Contribution to journalArticle

Abstract

Cytotoxic T lymphocytes (CTL) control the replication of human cytomegalovirus (CMV). Previous studies assessed the clonotypic composition of CTL specific for individual immunodominant peptides within a certain HLA context. Such an approach has inherent limitations and may not assess the true clonal CTL response in vivo. Here, the clonotypic composition of CMV-specific CTL was determined in HLA-A2, CMV-seropositive kidney transplant recipients and healthy blood donors after stimulation of peripheral blood mononuclear cells with either a pp65 whole-peptide pool or a single immunodominant peptide. Even after stimulation with the whole peptide pool, CMV-specific CTL remained monoclonal or oligoclonal. Regarding intraindividual variation, the CDR3 motifs of the dominant clones were identical to those observed in CTL generated by the single immunodominant peptide. Sequencing of the CDR3 regions demonstrated significant interindividual variation; however, structural homology was observed for immunodominant clonotypes in three individuals. In conclusion, the highly focused T cell receptor repertoire found after stimulation with either a single immunodominant peptide or a peptide pool demonstrates a pivotal role for immunodominant epitopes in the generation of a clonal repertoire. These results provide new insights into the regulation of CMV clonal dominance and may contribute to the design and monitoring of adoptive immunotherapy.

Original languageEnglish (US)
Pages (from-to)344-352
Number of pages9
JournalJournal of the American Society of Nephrology
Volume20
Issue number2
DOIs
StatePublished - Feb 2009
Externally publishedYes

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Cytotoxic T-Lymphocytes
Cytomegalovirus
Peptides
HLA-A2 Antigen
Adoptive Immunotherapy
Immunodominant Epitopes
T-Cell Antigen Receptor
Blood Donors
Blood Cells
Clone Cells
Kidney

ASJC Scopus subject areas

  • Nephrology

Cite this

Babel, N., Brestrich, G., Gondek, L., Sattler, A., Wlodarski, M. W., Poliak, N., ... Maciejewski, J. P. (2009). Clonotype analysis of cytomegalovirus-specific cytotoxic T lymphocytes. Journal of the American Society of Nephrology, 20(2), 344-352. https://doi.org/10.1681/ASN.2007111225

Clonotype analysis of cytomegalovirus-specific cytotoxic T lymphocytes. / Babel, Nina; Brestrich, Gordon; Gondek, Lukasz; Sattler, Arne; Wlodarski, Marcin W.; Poliak, Nina; Bethke, Nicole; Thiel, Andreas; Hammer, Markus H.; Reinke, Petra; Maciejewski, Jaroslaw P.

In: Journal of the American Society of Nephrology, Vol. 20, No. 2, 02.2009, p. 344-352.

Research output: Contribution to journalArticle

Babel, N, Brestrich, G, Gondek, L, Sattler, A, Wlodarski, MW, Poliak, N, Bethke, N, Thiel, A, Hammer, MH, Reinke, P & Maciejewski, JP 2009, 'Clonotype analysis of cytomegalovirus-specific cytotoxic T lymphocytes', Journal of the American Society of Nephrology, vol. 20, no. 2, pp. 344-352. https://doi.org/10.1681/ASN.2007111225
Babel, Nina ; Brestrich, Gordon ; Gondek, Lukasz ; Sattler, Arne ; Wlodarski, Marcin W. ; Poliak, Nina ; Bethke, Nicole ; Thiel, Andreas ; Hammer, Markus H. ; Reinke, Petra ; Maciejewski, Jaroslaw P. / Clonotype analysis of cytomegalovirus-specific cytotoxic T lymphocytes. In: Journal of the American Society of Nephrology. 2009 ; Vol. 20, No. 2. pp. 344-352.
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