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Journal of Virology, October 2009, p. 9803-9812, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00776-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Diverse Cross-Reactive Potential and Vβ Gene Usage of an Epitope-Specific Cytotoxic T-Lymphocyte Population in Monkeys Immunized with Diverse Human Immunodeficiency Virus Type 1 Env Immunogens{triangledown}

Sandrine L. Hulot, Michael S. Seaman, Pritha Sen, Patrick A. Autissier, Edwin R. Manuel, and Norman L. Letvin*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, Massachusetts 02215

Received 16 April 2009/ Accepted 16 July 2009

An ideal human immunodeficiency virus type 1 (HIV-1) vaccine would elicit potent cellular and humoral immune responses that recognize diverse strains of the virus. In the present study, combined methodologies (flow cytometry, Vβ repertoire analysis, and complementarity-determining region 3 sequencing) were used to determine the clonality of CD8+ T lymphocytes taking part in the recognition of variant epitope peptides elicited in Mamu-A*01-positive rhesus monkeys immunized with vaccines encoding diverse HIV-1 envelopes (Envs). Monkeys immunized with clade B Envs generated CD8+ T lymphocytes that cross-recognized both clade B- and clade C-p41A epitope peptides using a large degree of diversity in Vβ gene usage. However, with two monkeys immunized with clade C Env, one monkey exhibited p41A-specific cytotoxic T-lymphocytes (CTL) with the capacity for cross-recognition of variant epitopes, while the other monkey did not. These studies demonstrate that the cross-reactive potential of variant p41A epitope peptide-specific CTL populations can differ between monkeys that share the same restricting major histocompatibility complex class I molecule and receive the same vaccine immunogens.

* Corresponding author. Mailing address: Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 735-4400. Fax: (617) 735-4527. E-mail: nletvin{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 29 July 2009.

Journal of Virology, October 2009, p. 9803-9812, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00776-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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