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Journal of Virology, December 2006, p. 12032-12040, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01479-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Contribution of T-Cell Receptor Repertoire Breadth to the Dominance of Epitope-Specific CD8+ T-Lymphocyte Responses{triangledown}

Edwin R. Manuel,1 William A. Charini,1 Pritha Sen,1 Fred W. Peyerl,1 Marcelo J. Kuroda,1 Jörn E. Schmitz,1 Patrick Autissier,1 Dennis A. Sheeter,2 Bruce E. Torbett,2 and Norman L. Letvin1*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, Massachusetts 02215,1 Department of Molecular and Experimental Medicine (L55), 10550 North Torrey Pines Rd., The Scripps Research Institute, La Jolla, California 920372

Received 12 July 2006/ Accepted 28 September 2006

Dominant epitope-specific CD8+ T-lymphocyte responses play a central role in controlling viral spread. We explored the basis for the development of this focused immune response in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys through the use of two dominant (p11C and p199RY) and two subdominant (p68A and p56A) epitopes. Using real-time PCR to quantitate T-cell receptor (TCR) variable region beta (Vß) family usage, we show that CD8+ T-lymphocyte populations specific for dominant epitopes are characterized by a diverse Vß repertoire, whereas those specific for subdominant epitopes employ a dramatically more focused Vß repertoire. We also demonstrate that dominant epitope-specific CD8+ T lymphocytes employ TCRs with multiple CDR3 lengths, whereas subdominant epitope-specific cells employ TCRs with a more restricted CDR3 length. Thus, the relative dominance of an epitope-specific CD8+ T-lymphocyte response reflects the clonal diversity of that response. These findings suggest that the limited clonal repertoire of subdominant epitope-specific CD8+ T-lymphocyte populations may limit the ability of these epitope-specific T-lymphocyte populations to expand and therefore limit the ability of these cell populations to contribute to the control of viral replication.

* Corresponding author. Mailing address: Beth Israel Deaconess Medical Center, 41 Ave. Louis Pasteur, Boston, MA 02115. Phone: (617) 667-2766. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu.

{triangledown} Published ahead of print on 11 October 2006.

Journal of Virology, December 2006, p. 12032-12040, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01479-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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