A shared MHC supertype motif emerges by convergent evolution in macaques and mice, but is totally absent in human MHC molecules

Alessandro Sette, John Sidney, Scott Southwood, Carrie Moore, Jessica Berry, Courtney Dow, Kate Bradley, Ilka Hoof, Mark G. Lewis, William H. Hildebrand, Curtis P. McMurtrey, Nancy A. Wilson, David I. Watkins, Bianca R. Mothé

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


The SIV-infected rhesus macaque (Macaca mulatta) is the most established model of AIDS disease systems, providing insight into pathogenesis and a model system for testing novel vaccines. The understanding of cellular immune responses based on the identification and study of Major Histocompatibility Complex (MHC) molecules, including their MHC:peptide-binding motif, provides valuable information to decipher outcomes of infection and vaccine efficacy. Detailed characterization of Mamu-B*039:01, a common allele expressed in Chinese rhesus macaques, revealed a unique MHC:peptidebinding preference consisting of glycine at the second position. Peptides containing a glycine at the second position were shown to be antigenic from animals positive for Mamu-B*039:01. A similar motif was previously described for the D d mouse MHC allele, but for none of the human HLA molecules for which a motif is known. Further investigation showed that one additional macaque allele, present in Indian rhesus macaques, Mamu-B*052:01, shares this same motif. These "G2" alleles were associated with the presence of specific residues in their B pocket. This pocket structure was found in 6% of macaque sequences but none of 950 human HLA class I alleles. Evolutionary studies using the "G2" alleles points to common ancestry for the macaque sequences, while convergent evolution is suggested when murine and macaque sequences are considered. This is the first detailed characterization of the pocket residues yielding this specific motif in nonhuman primates and mice, revealing a new supertype motif not present in humans.

Original languageEnglish (US)
Pages (from-to)421-434
Number of pages14
Issue number6
StatePublished - Jun 2012
Externally publishedYes


  • HLA supertype
  • MHC
  • Peptide-binding motif
  • Rhesus macaque

ASJC Scopus subject areas

  • Immunology
  • Genetics


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