A Novel, Nonclassical MHC Class I Molecule Specific to the Common Chimpanzee

Abstract

All expressed human MHC class I genes (HLA-A, -B, -C, -E, -F, and -G) have functional orthologues in the MHC of the common chimpanzee (Pan troglodytes). In contrast, a nonclassical MHC class I gene discovered in the chimpanzee is not present in humans or the other African ape species. In exons and more so in introns, this Patr-AL gene is similar to the expressed A locus in the orangutan, Popy-A, suggesting they are orthologous. Patr-AL/Popy-A last shared a common ancestor with the classical MHC-A locus >20 million years ago. Population analysis revealed little Patr-AL polymorphism: just three allotypes differing only at residues 52 and 91. Patr-AL is expressed in PBMC and B cell lines, but at low level compared with classical MHC class I. The Patr-AL polypeptide is unusually basic, but its glycosylation, association with β2-microglobulin, and antigenicity at the cell surface are like other MHC class I. No Patr-AL-mediated inhibition of polyclonal chimpanzee NK cells was detected. The Patr-AL gene is present in 50% of chimpanzee MHC haplotypes, correlating with presence of a 9.8-kb band in Southern blots. The flanking regions of Patr-AL contain repetitive/retroviral elements not flanking other class I genes. In sequenced HLA class I haplotypes, a similar element is present in the A*2901 haplotype but not the A*0201 or A*0301 haplotypes. This element, 6 kb downstream of A*2901, appears to be the relic of a human gene related to Patr-AL. Patr-AL has characteristics of a class I molecule of innate immunity with potential to provide common chimpanzees with responses unavailable to humans.

Unparalleled complexity of the MHC class I region in rhesus macaques

“…The Mamu-A*05͞*24 locus (proposed name Mamu-A2), characterized by differential distribution, might encode a nonclassical class I protein with a specialized function in the immune response. A similar situation may exist for the Patr-AL locus in chimpanzees (30).…”

NK Cell Receptors of the Orangutan (Pongo pygmaeus): A Pivotal Species for Tracking the Coevolution of Killer Cell Ig-Like Receptors with MHC-C

“…Although Popy-E and -G may indeed represent orthologs of the human genes, the properties of Popy-A, -B, and -C imply less straightforward, paralogous relationships. Popy-A appears less related to HLA-A and Patr-A than to Patr-AL, a nonclassical class I gene present on some chimpanzee MHC haplotypes (15). Unlike HLA-A or Patr-A, which are fixed, Popy-C is present on ϳ50% of Popy-MHC haplotypes (14); but in contrast, Popy-B appears duplicated such that individual orangutans express three or four Popy-B alleles (14,44).…”

“…Being more divergent from humans than the chimpanzee, the orangutan has an MHC in which the class I genes have several defined differences from their human counterparts (11). Whereas Popy-E and -G are orthologous (12,13), the Popy-A and -B genes may not be orthologs of HLA-A and -B (14,15). Most important is that the Popy-C locus is only present on ϳ50% of MHC haplotypes; and thus, a significant minority of orangutans lack an MHC-C locus (14).…”

Gorilla MHC class I gene and sequence variation in a comparative context

“…Comparative analysis of a single gorilla MHC haplotype showed that Gogo-Oko is syntenic to the chimpanzee A -related locus Patr-AL (Gleimer et al 2011). Patr-AL is present on only half of the surveyed chimpanzee MHC haplotypes and is in strong linkage disequilibrium with Patr-A , the chimpanzee orthologue of HLA-A (Adams et al 2001; Geller et al 2002). In contrast, the gorilla MHC haplotype with Gogo-Oko lacks the genomic block containing the A locus (Gleimer et al 2011).…”