The pigtail macaque MHC class I allele Mane-A*10 presents an immunodominant SIV Gag epitope: Identification, tetramer development and implications of immune escape and reversion

Miranda Z. Smith, Caroline S. Fernandez, Amy Chung, C. Jane Dale, Robert De Rose, Jie Lin, Andrew G. Brooks, Kendall C. Krebs, David Watkins, David H. O'Connor, Miles P. Davenport, Stephen J. Kent

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The pigtail macaque (Macaca nemestrina) is a common model for the study of AIDS. The pigtail major histocompatibility complex class I allele Mane-A*10 restricts an immunodominant simian immunodeficiency virus (SIV) Gag epitope (KP9) which rapidly mutates to escape T cell recognition following acute simian/human immunodeficiency virus infection. Two technologies for the detection of Mane-A*10 in outbred pigtail macaques were developed: reference strand-mediated conformational analysis and sequence-specific primer polymerase chain reaction. A Mane-A*10/K-P9 tetramer was then developed to quantify CD8+ T lymphocytes primed by multigenic DNA vaccination, which have previously been difficult to detect using standard interferon-γ-based T cell assays. We also demonstrate mutational escape at KP9 following acute SIV infection. Mane-A*10+ animals have lower set point SIV levels than Mane-A*10- animals, suggesting a significant fitness cost of escape. These studies pave the way for a more robust understanding of HIV vaccines in pigtail macaques.

Original languageEnglish
Pages (from-to)282-293
Number of pages12
JournalJournal of Medical Primatology
Volume34
Issue number5-6 SPEC. ISS.
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

    Fingerprint

Keywords

  • CD8 T cells
  • Major histocompatibility complex typing
  • Tetramer
  • Vaccines
  • Viral escape

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

Cite this

Smith, M. Z., Fernandez, C. S., Chung, A., Dale, C. J., De Rose, R., Lin, J., Brooks, A. G., Krebs, K. C., Watkins, D., O'Connor, D. H., Davenport, M. P., & Kent, S. J. (2005). The pigtail macaque MHC class I allele Mane-A*10 presents an immunodominant SIV Gag epitope: Identification, tetramer development and implications of immune escape and reversion. Journal of Medical Primatology, 34(5-6 SPEC. ISS.), 282-293. https://doi.org/10.1111/j.1600-0684.2005.00126.x