Mamu-I: A Novel Primate MHC Class I B-Related Locus with Unusually Low Variability

• Published in: The Journal of immunology (1950) Vol. 164; no. 3; pp. 1386 - 1398
• Main Authors: Urvater, Julie A, Otting, Nel, Loehrke, Jamie H, Rudersdorf, Richard, Slukvin, Igor I, Piekarczyk, Marian S, Golos, Thaddeus G, Hughes, Austin L, Bontrop, Ronald E, Watkins, David I
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.2000
• Subjects: Alleles; Amino Acid Sequence; Animals; B-Lymphocytes - metabolism; Base Sequence; Cell Line, Transformed; Evolution, Molecular; Gene Duplication; Genes, MHC Class I; Genetic Markers - immunology; Genetic Variation - genetics; Genetic Variation - immunology; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - genetics; histocompatibility locus Mamu; Isoelectric Focusing; Macaca mulatta - genetics; Macaca mulatta - immunology; Molecular Sequence Data; Organ Specificity - genetics; Polymorphism, Genetic - immunology; RNA, Messenger - genetics; Sequence Homology, Nucleic Acid; Transfection
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.3.1386

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 humans, lymphocytes from a single rhesus macaque express up to 12 different MHC class I cDNAs. From which locus these various alleles are derived is unclear. In our attempts to define the MHC class I loci of the rhesus macaque, we have identified an unusual MHC class I locus, Mamu-I. We isolated 26 I locus alleles from three different macaque species but not from three other Cercopithecine genera, suggesting that the I locus is the result of a recent duplication of the B locus occurring after the divergence of macaques from the ancestor of the other extant Cercopithecine genera. Mamu-I mRNA transcripts were detected in all tissues examined and Mamu-I protein was produced in rhesus B lymphoblastoid cell lines. Furthermore, Mamu-I protein was detected 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 is unusually low sequence variability, with the mean number of nucleotide differences between alleles being only 3.6 nt. Therefore, Mamu-I is less variable than any other polymorphic MHC class I locus described to date. Additionally, no evidence for positive selection on the peptide binding region was observed. Together, these results suggest that Mamu-I is an MHC class I locus in primates that has features of both classical and nonclassical loci.