Mamu-A and Mamu-B loci in macaques are genetically unstable and have undergone a complex series of duplications. Unlike HLA class I haplotypes in humans, where three loci (HLA-A, HLA-B, HLA-C) each encode a single allele (e.g., the HLA-B locus on the maternal haplotype encodes HLA-B*27:01 and the HLA-B locus on the paternal haplotype encodes HLA-B*41:01), a single macaque haplotype may have more than 20 MHC class I genes. Not all of these genes encode molecules that are stably expressed on the cell surface. This means that an animal might have one haplotype with 10 functional MHC class I alleles and a second haplotype with 6 functional MHC class I alleles, for a total of 16 expressed MHC class I molecules.
A simplified cartoon of the macaque MHC class I region is shown below (there are actually more Mamu-A and Mamu-B loci on each haplotype than in the cartoon). The blue shaded boxes represent those genes expressed on the paternal haplotype while the pink shaded boxes indicate genes expressed on the maternal haplotype.
In this example, the macaque would express 11 distinct MHC class I transcripts (4 Mamu-A alleles and 7 Mamu-B alleles). These genes are inherited as haplotypes, or defined groups of alleles, from the parents. We generally consider the Mamu-A and Mamu-B haplotypes independent from each other, since the MHC class I A and I B regions are separated by ~1 Mb which allows for relatively frequent recombination to occur on a population basis.
The variable number of MHC lineages expressed by each macaque are detected over a wide range of transcript abundance when sequencing from RNA templates. ‘Major’ alleles account for the preponderance of total transcripts detected and we assume the bulk of immune responses would be dictated by the complement of ‘major’ alleles expressed by each macaque. A schematic of the reduction of a set of specific alleles down to the final haplotype designation for an example Mamu-A haplotype is shown below:
Names are assigned to each haplotype based on the presence of a diagnostic major lineage, typically the most transcriptionally abundant allele contained on a haplotype but occasionally selected based on known biological significance (i.e., the B017 haplotype). Different versions of a base haplotype, denoted with a lowercase letter following the haplotype name (for instance, B001a and B001b), result when there are differences in the complement of major lineages accompanying the diagnostic allele.
Haplotype definitions are available for rhesus and cynomolgus macaques; pig-tailed macaque haplotype designations should be available in late 2015.