The MHC E locus in macaques is polymorphic and is conserved between macaques and humans

Boyson, Jonathan E.; McAdam, Stephen N.; Gallimore, Awen; Golos, Thaddeus G.; Liu, Xiaomin; Gotch, Frances; Hughes, Austin L.; Watkins, David I.

doi:10.1007/bf00182314

Cited by 88 publications

(62 citation statements)

References 54 publications

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“…In humans, the ligand for these receptors is the nonclassical MHC class I HLA-E molecule (33). The homologue of HLA-E, Mamu-E, has also been identified in rhesus monkeys (34). Because HLA-E homologues in primates have limited polymorphism and are the most phylogenetically conserved of the MHC class I genes, it is not surprising that the NKG2 family is more conserved than the KIR molecules (35).…”

Section: Discussionmentioning

confidence: 99%

Diversity of the Killer Cell Ig-Like Receptors of Rhesus Monkeys

Hershberger

Shyam

Miura

et al. 2001

The Journal of Immunology

118

168

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Because the killer cell Ig-like receptors (KIRs) have only been characterized in humans and chimpanzees, we do not have a full understanding of their evolutionary history. Therefore, cDNAs encoding the KIR molecules of five rhesus monkeys were characterized, and were found to differ from the KIR molecules identified in humans and chimpanzees. Whereas only one KIR2DL4 molecule is detected in humans and chimpanzees, two distinct KIR2DL4 homologues were identified in the monkeys. Although the two human KIR3DL molecules are limited in their polymorphism, the KIR3DL homologues in the monkeys were highly polymorphic. Up to five KIR3DL homologues were identified in each monkey that was studied, and eleven distinct KIR3DL molecules were detected in the five rhesus monkeys. Two novel families of KIR molecules were identified in the rhesus monkeys, KIR3DH and KIR1D. The KIR3DH molecules have three Ig domains, transmembrane domains homologous to KIR2DL4 molecules that contain an arginine, and short cytoplasmic domains. With these features, the KIR3DH molecules resemble the activating forms of the human KIR molecules. The KIR1D molecule encodes only one complete Ig domain before a frame-shift in the second Ig domain occurs, leading to early termination of the molecule. Multiple splice variants of KIR1D exist that encode at least one Ig domain, as well as transmembrane and cytoplasmic domains. The extensive diversity of the rhesus monkey KIR3DL homologues and the novel KIR3DH and KIR1D molecules suggests that the KIR family of molecules has evolved rapidly during the evolution of primates.

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Section: Discussionmentioning

confidence: 99%

Diversity of the Killer Cell Ig-Like Receptors of Rhesus Monkeys

Hershberger

Shyam

Miura

et al. 2001

The Journal of Immunology

118

168

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“…We isolated two Mamu-I alleles in addition to other Mamu-B alleles in the offspring of two adult macaques, and the alleles of this locus were segregated and inherited in a Mendelian fashion, suggesting that they represented alleles of a separate locus. Because MHC class I A-H loci already exist in primates (8,(17)(18)(19)35), we have called this new locus Mamu-I in accordance with established nomenclature guidelines (25). We were unable to detect an I locus on the a haplotype (Fig.…”

Section: Alleles At This New Locus Are Inherited In a Mendelian Fashionmentioning

confidence: 99%

“…It is now becoming increasingly clear that the MHC class I locus of the rhesus macaque is much more complex than its human counterpart. Orthologs of the human HLA-A, -B, -E, -F, and -G loci have now been indentified in the rhesus monkey (8,(17)(18)(19). However, there is also evidence to suggest that the Mamu-A and Mamu-B loci have duplicated at least once (8).…”

Section: Figurementioning

confidence: 99%

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

Urvater¹,

Otting

Loehrke³

et al. 2000

The Journal of Immunology

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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.

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“…Molecular studies of class I have defined expressed orthologs to the HLA-A and HLA-B loci (Miller et al 1991;Boyson et al 1996), including evidence that both the mamu-A and mamu-B loci have been duplicated with as many as three B and two A loci detected in certain haplotypes (Boyson et al 1996;Urvater et al 2000). Homologs of the human nonclassical class I antigens HLA-E and HLA-F were described (Otting and Bontrop 1993; Knapp et al 1998) and a functional homolog of HLA-G termed mamu-AG was characterized (Otting and Bontrop 1993;Boyson et al 1995;Ryan et al 2002). Humans and rhesus share most MHC class II loci including -DR, -DQ, and -DP, and an increase in the number of DRB genes in some rhesus haplotypes has been suggested (Slierendregt et al 1994).…”

mentioning

confidence: 99%

Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

Daza-Vamenta¹,

Glusman²,

Rowen³

et al. 2004

Genome Res.

201

255

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The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque.

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The MHC E locus in macaques is polymorphic and is conserved between macaques and humans

Cited by 88 publications

References 54 publications

Diversity of the Killer Cell Ig-Like Receptors of Rhesus Monkeys

Diversity of the Killer Cell Ig-Like Receptors of Rhesus Monkeys

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

Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

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