2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2007111225v1 20/2/344    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Babel, N. Articles by Maciejewski, J. P. Search for Related Content PubMed PubMed Citation Articles by Babel, N. Articles by Maciejewski, J. P.

Clonotype Analysis of Cytomegalovirus-Specific Cytotoxic T Lymphocytes

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

^* Experimental Haematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and Department of Nephrology, Berlin-Brandenburg-Center for Regenerative Therapies, Charité University Medicine Berlin, Campus Virchow Clinic, and German Rheumatism Research Center, Berlin, Germany

Correspondence: Dr. Nina Babel, Department of Nephrology, Charité University Medicine Berlin, Campus Virchow Clinic, Augustenburger Platz 1, 13353 Berlin, Germany. Phone: +4930-450-653880; Fax: +4930-450-552922; E-mail: nina.babel{at}charite.de

Received for publication November 20, 2007. Accepted for publication June 25, 2008.

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.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673