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Aim: Humans and orangutans shared a common ancestor about 12-16 million years ago. Two orangutan species are officially recognized; one inhabiting Borneo (Pongo pygmaeus) and the other Sumatra (Pongo abelii). Orangutans possess A, B, and C genes that are homologous to their HLA equivalents. Unlike humans where each of these is found as a single copy gene on a haplotype, orangutan haplotypes may possess a duplicated B gene whereas others lack C. In theory, orangutans may express from 3 to 8 different classical MHC class I allotypes. Conventional sequencing of cDNA derived from six different orangutan samples, using 4 different primer sets, suggested that certain alleles, in particular MHC-C, are less well transcribed. Therefor we aimed to investigate the transcription/expression profile of the orangutan MHC class I genes. Methods: cDNA, derived from five different orangutan EBV transformed B-cell-lines (two Popy and three Poab), was used as starting material. Generic primers were designed, and relevant amplicons were sequenced in both directions using massively parallel sequencing. Results: The analyses showed that the A locus is most abundantly transcribed. The B locus exhibits differential transcription patterns that seem to be dependent on the B allotype present in an animal. The present analyses show an almost negligible transcription of the B∗03-locus/lineage. In addition, the C locus, if present, appears to be minutely transcribed. Moreover, the cell-surface expression of several MHC allotypes was assessed using various monoclonal antibodies. Conclusions: The present data suggest a minor immunological role for B∗03-lineage and C-locus molecules in orangutangs as they appear to be virtually absent on peripheral blood derived cells. Besides, all animals investigated transcribe at least one variant of the B∗08-lineage that encodes the C1-epitope, the ligand for particular killer cell Ig-like receptor, and most likely compensate for the partial loss of the C-locus in orangutans. [Copyright &y& Elsevier]

Abstract: In most primate species, the class II region of the Major Histocompatibility Complex (MHC) displays diversity with regard to gene copy number and combination of DRB genes present per region configuration. Some of these loci exhibit extremely high levels of allelic variability, whereas others display only moderate levels of polymorphism. To understand the evolutionary history of the various HLA-DR region genes, a large number of full-length sequences of rhesus macaques, chimpanzees and humans were determined. The exon–intron organisation of the DRA gene, displaying only low levels of polymorphism, appears to have been highly conserved during primate evolution. The physical length of various DRB genes/alleles, however, fluctuates significantly in primates due to the presence of indels (insertions/deletions), mainly mapping to intron 1. Phylogenetic evidence supports the notion that the generation of new DRB genes is a dynamic and steadily ongoing process. Indeed, most of the primate DRB alleles investigated represent relatively young entities, possessing species-unique sequences. This seems to contradict the current view that the highly similar peptide binding motifs of many HLA-, Patr- and Mamu-DR molecules, encoded by exon 2 of the DRB gene, represent old entities, which predate primate speciation. As no evidence was found for convergent evolution, the combination of these two observations indicates that ancient peptide binding motifs are frequently reshuffled among duplicated members of the HLA-DRB multigene family. [Copyright &y& Elsevier]