Mamu-I: A novel primate MHC class IB-related locus with unusually low variability

The rhesus macaque is an important animal model for several human diseases and organ transplantation. Therefore, definition of the MHC of this species is crucial to the development of these models. Unfortunately, unlike human s, lymphocytes from a single rhesus macaque express up to 12 different MHC class I cDNAs, From which locus these various alleles are derived is unclea r. In our attempts to define the MHC class I loci of the rhesus macaque, we have identified an unusual MI-IC class I locus, Mamu-I. We isolated 26 I l ocus alleles from three different macaque species but not from three other Cercopithecine genera, suggesting that the I locus is the result of a recen t duplication of the B locus occurring after the divergence of macaques fro m the ancestor of the other extant Cercopithecine genera, Mamu-I mRNA trans cripts were detected in all tissues examined and Mamu-I protein was produce d in rhesus B lymphoblastoid cell lines, Furthermore, Mamu-I protein was de tected by flow cytometry on the surface of human 721.221 cells transfected with Mamu-I. In contrast to the polymorphism present at this locus, there i s unusually low sequence variability, with the mean number of nucleotide di fferences between alleles being only 3.6 nt, Therefore, Mamu-I is less vari able than any other polymorphic MHC class I locus described to date. Additi onally, no evidence for positive selection on the peptide binding region wa s observed. Together, these results suggest that Mamu-I is an MHC class I l ocus in primates that has features of both classical and nonclassical loci.