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Journal of Virology, January 2001, p. 738-749, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.738-749.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

CD8+ Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing

Todd M. Allen,1 Bianca R. Mothé,1,2 John Sidney,3 Peicheng Jing,1 John L. Dzuris,3 Max E. Liebl,1 Thorsten U. Vogel,1 David H. O'Connor,1 Xiaochi Wang,4 Michael C. Wussow,1 James A. Thomson,1 John D. Altman,4 David I. Watkins,1,2,* and Alessandro Sette3

Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 537151; Epimmune, San Diego, California 921213; Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia4; and Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53706-15322

Received 6 June 2000/Accepted 18 October 2000

It is becoming increasingly clear that any human immunodeficiency virus (HIV) vaccine should induce a strong CD8+ response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene (or EpiGene) is a potential means to achieve these goals. To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8+ epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule. We had previously identified the peptide binding motif of Mamu-A*012, a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM). Herein, we scanned SIV proteins for the presence of Mamu-A*01 motifs. The binding capacity of 221 motif-positive peptides was determined using purified Mamu-A*01 molecules. Thirty-seven peptides bound with apparent Kd values of 500 nM or lower, with 21 peptides binding better than the Gag_CM9 peptide. Peripheral blood mononuclear cells from SIV-infected Mamu-A*01+ macaques recognized 14 of these peptides in ELISPOT, CTL, or tetramer analyses. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step toward the design of a multiepitope vaccine for SIV and HIV.

* Corresponding author. Mailing address: Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715-1299. Phone: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu.

Journal of Virology, January 2001, p. 738-749, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.738-749.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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