Pig-tailed macaques (Macaca nemestrina) possess six MHC-E families that are conserved among macaque species: implication for their binding to natural killer receptor variants

Abstract

MHC loci encode highly polymorphic molecules involved in the presentation of self and non-self peptides to cells of the adaptive and innate immune systems. Although variable, MHC-E genes are well conserved among primates and provide signals to natural killer cells. In this study, we sequenced and analyzed MHC-E alleles of pig-tailed macaque (Macaca nemestrina), a nonhuman primate used for HIV pathogenesis and vaccine studies. Among a group of seven macaques, the characterization of eight Mane-E alleles revealed an increased number of polymorphic sites compared with human HLA-E alleles. Phylogenetic analyses of MHC-E alleles from pig-tailed macaque, rhesus monkey (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis) demonstrated that the three macaque species shared six families of macaque MHC-E alleles and indicated that these families existed in the common ancestor 5.5 million years ago. Polymorphic Mane-E sites were not concentrated within the peptide-binding pockets, but were distributed throughout the entire ORF. The peptide-binding domain of Mane-E is similar to its human analogue, and peptide substrates theoretically capable of binding to Mane-E molecules were found in the leader sequence of classical Mane-A and -B molecules. Additionally, the polymorphic amino acids located in the alpha(1) and alpha(2) domains of Mane-E molecules have side chains expected to be oriented toward solvent and away from the peptide-binding groove, suggesting that some of them (positions 19, 73, 79 and 145) might be available for interaction with polymorphic receptors of natural killer cells.

Survey of major histocompatibility complex class II diversity in pig-tailed macaques

“…Of these, 73 alleles were mismatched at one or more bases from any sequences in the database of named alleles, 44 were extensions to previously identified named alleles, and only 11 matched named full-length sequences. Almost half of these sequences (61 of 128) are identical to alleles previously described in rhesus and/or cynomolgus macaques, which is consistent with previously observed sharing of pig-tailed macaque MHC class I sequences and high levels of MHC class II allele sharing between macaque species (Lafont et al 2004; Doxiadis et al 2006; O’Leary et al 2009; Creager et al 2011). …”

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing

“…All of the newly identified Mafa-E and Mafa-F alleles (tentatively named as Mafa-E-like1~Mafa-Elike11 and Mafa-F-like1~Mafa-F-like7) have 94.7 to 99.6 % and 98.7 to 99.6 % nucleotide similarities among the 473-bp peptide-binding region, respectively (ESM Table 2 Table 2). Of the 112 alleles, 13 alleles were perfectly matched with previously reported alleles of the rhesus macaque (Macaca mulatta, Mamu) (Boyson et al 1995;Boyson et al 1996;Campbell et al 2009;Karl et al 2008;Muhl et al 2002;Otting et al 2007;Otting et al 2005), the southern pig-tailed macaque (Macaca nemestrina, Mane) (Lafont et al 2003;Lafont et al 2004) and/or stump-tailed macaque (Macaca arctoides, Maar) (Urvater et al 2000). These trans-species polymorphisms (Table 3) were probably already generated before speciation of cynomolgus macaques 2.4~4.2 million years ago (Hedges et al 2006).…”

Identification of novel MHC class I sequences in pig-tailed macaques by amplicon pyrosequencing and full-length cDNA cloning and sequencing

“…The predicted amino acid sequences of the Mane transcripts described in this report exhibit a high degree of homology to MHC transcripts characterized in rhesus and cynomolgus macaques, despite the fact that pig-tailed macaques belong to a distinct evolutionary clade (silenus ) that diverged over five million years ago from the fasicularis clade which gave rise to both rhesus and cynomolgus macaques (Tosi et al 2000; Deinard & Smith 2001; Li et al 2009). Previously, the most notable example of conserved MHC class I protein sequences between pig-tailed macaques and the more closely related rhesus and cynomolgus macaques was the observed sequence homology of nonclassical MHC class I sequences (Lafont et al 2003; Lafont et al 2004). Among the novel Mane-B transcripts characterized here, twenty are 100% identical in the peptide binding region to Mamu or Mafa gene products, and twelve of these transcripts are identical to their Mamu or Mafa homologues throughout the complete protein translation.…”