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Journal of Virology, September 2000, p. 8751-8756, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 Envelope Epitope-Specific CD4⁺ T Lymphocytes in Simian/Human Immunodeficiency Virus-Infected and Vaccinated Rhesus Monkeys Detected Using a Peptide-Major Histocompatibility Complex Class II Tetramer

Marcelo J. Kuroda,^1,* Jörn E. Schmitz,¹ Christine Lekutis,¹ Christine E. Nickerson,¹ Michelle A. Lifton,¹ Genoveffa Franchini,² Janet M. Harouse,³ Cecilia Cheng-Mayer,³ and Norman L. Letvin¹

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215¹; Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892²; and Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016³

Received 30 March 2000/Accepted 19 June 2000

A tetrameric recombinant major histocompatibility complex (MHC) class II-peptide complex was used to quantitate human immunodeficiency virus type 1 (HIV-1) envelope (Env)-specific CD4⁺ T cells in vaccinated and in simian/human immunodeficiency virus (SHIV)-infected rhesus monkeys. A rhesus monkey MHC class II DR molecule, Mamu-DR*W201, and an HIV-1 Env peptide (p46) were employed to construct this tetrameric complex. A p46-specific proliferative response was seen in sorted, tetramer-binding, but not nonbinding, CD4⁺ T cells, directly demonstrating that this response was mediated by the epitope-specific lymphocytes. Although staining of whole blood from 10 SHIV-infected Mamu-DR*W201⁺ rhesus monkeys failed to demonstrate tetramer-binding CD4⁺ T cells (<0.02%), p46-stimulated peripheral blood mononuclear cells (PBMCs) from 9 of these 10 monkeys had detectable p46 tetramer-binding cells, comprising 0.5 to 15.2% of the CD4⁺ T cells. p46-stimulated PBMCs from 7 of 10 Mamu-DR*W201⁺ monkeys vaccinated with a recombinant canarypox virus-HIV-1 env construct also demonstrated p46 tetramer-binding cells, comprising 0.9 to 7.2% of the CD4⁺ T cells. Thus, Env p46-specific CD4⁺ T cells can be detected by tetrameric Mamu-DR*W201-p46 complex staining of PBMCs in both SHIV-infected and vaccinated rhesus monkeys. These epitope-specific cell populations appear to be present in peripheral blood at a very low frequency.

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^* Corresponding author. Mailing address: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE-102, P.O. Box 15732, Boston, MA 02215. Phone: (617) 667-1795. Fax: (617) 667-8210. E-mail: mkuroda{at}caregroup.harvard.edu.

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Journal of Virology, September 2000, p. 8751-8756, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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