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Journal of Virology, January 2005, p. 684-695, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.684-695.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Analysis of Pigtail Macaque Major Histocompatibility Complex Class I Molecules Presenting Immunodominant Simian Immunodeficiency Virus Epitopes

Miranda Z. Smith,1 C. Jane Dale,1 Robert De Rose,1 Ivan Stratov,1 Caroline S. Fernandez,1 Andrew G. Brooks,1 Jason Weinfurter,2 Kendall Krebs,2 Cara Riek,2 David I. Watkins,2 David H. O'Connor,2 and Stephen J. Kent1*

Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia,1 Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin2

Received 15 June 2004/ Accepted 3 September 2004

Successful human immunodeficiency virus (HIV) vaccines will need to induce effective T-cell immunity. We studied immunodominant simian immunodeficiency virus (SIV) Gag-specific T-cell responses and their restricting major histocompatibility complex (MHC) class I alleles in pigtail macaques (Macaca nemestrina), an increasingly common primate model for the study of HIV infection of humans. CD8+ T-cell responses to an SIV epitope, Gag164-172KP9, were present in at least 15 of 36 outbred pigtail macaques. The immunodominant KP9-specific response accounted for the majority (mean, 63%) of the SIV Gag response. Sequencing from six macaques identified 7 new Mane-A and 13 new Mane-B MHC class I alleles. One new allele, Mane-A*10, was common to four macaques that responded to the KP9 epitope. We adapted reference strand-mediated conformational analysis (RSCA) to MHC class I genotype M. nemestrina. Mane-A*10 was detected in macaques presenting KP9 studied by RSCA but was absent from non-KP9-presenting macaques. Expressed on class I-deficient cells, Mane-A*10, but not other pigtail macaque MHC class I molecules, efficiently presented KP9 to responder T cells, confirming that Mane-A*10 restricts the KP9 epitope. Importantly, naïve pigtail macaques infected with SIVmac251 that respond to KP9 had significantly reduced plasma SIV viral levels (log10 0.87 copies/ml; P = 0.025) compared to those of macaques not responding to KP9. The identification of this common M. nemestrina MHC class I allele restricting a functionally important immunodominant SIV Gag epitope establishes a basis for studying CD8+ T-cell responses against AIDS in an important, widely available nonhuman primate species.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia. Phone: 61-383449939. Fax: 61-383443846. E-mail: skent{at}unimelb.edu.au.

Journal of Virology, January 2005, p. 684-695, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.684-695.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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