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

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.