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Journal of Virology, June 2009, p. 6011-6019, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00199-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mauritian Cynomolgus Macaques Share Two Exceptionally Common Major Histocompatibility Complex Class I Alleles That Restrict Simian Immunodeficiency Virus-Specific CD8⁺ T Cells ^,

Benjamin J. Burwitz,¹ Chad J. Pendley,² Justin M. Greene,¹ Ann M. Detmer,² Jennifer J. Lhost,¹ Julie A. Karl,² Shari M. Piaskowski,¹ Richard A. Rudersdorf,¹ Lyle T. Wallace,¹ Benjamin N. Bimber,¹ John T. Loffredo,¹ Daryl G. Cox,³ Wilfried Bardet,³ William Hildebrand,³ Roger W. Wiseman,² Shelby L. O'Connor,¹ and David H. O'Connor^1,2*

Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin 53706,¹ Wisconsin National Primate Research Center, Madison, Wisconsin 53706,² Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104³

Received 27 January 2009/ Accepted 25 March 2009

Vaccines that elicit CD8⁺ T-cell responses are routinely tested for immunogenicity in nonhuman primates before advancement to clinical trials. Unfortunately, the magnitude and specificity of vaccine-elicited T-cell responses are variable in currently utilized nonhuman primate populations, owing to heterogeneity in major histocompatibility (MHC) class I genetics. We recently showed that Mauritian cynomolgus macaques (MCM) have unusually simple MHC genetics, with three common haplotypes encoding a shared pair of MHC class IA alleles, Mafa-A*25 and Mafa-A*29. Based on haplotype frequency, we hypothesized that CD8⁺ T-cell responses restricted by these MHC class I alleles would be detected in nearly all MCM. We examine here the frequency and functionality of these two alleles, showing that 88% of MCM express Mafa-A*25 and Mafa-A*29 and that animals carrying these alleles mount three newly defined simian immunodeficiency virus-specific CD8⁺ T-cell responses. The epitopes recognized by each of these responses accumulated substitutions consistent with immunologic escape, suggesting these responses exert antiviral selective pressure. The demonstration that Mafa-A*25 and Mafa-A*29 restrict CD8⁺ T-cell responses that are shared among nearly all MCM indicates that these animals are an advantageous nonhuman primate model for comparing the immunogenicity of vaccines that elicit CD8⁺ T-cell responses.

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* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Dr., Madison, WI 53711. Phone: (608) 265-3389. Fax: (608) 265-8084. E-mail: doconnor{at}primate.wisc.edu

Published ahead of print on 1 April 2009.

Supplemental material for this article may be found at http://jvi.asm.org/.

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Journal of Virology, June 2009, p. 6011-6019, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00199-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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