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

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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/KP9 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.

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