Characterization and Phylogenetic Relationship of Prosimian MHC Class I Genes

Flügge, Perris; Zimmermann, Elke; Hughes, Austin L.; Günther, Eberhard; Walter, Lutz

doi:10.1007/s00239-002-2372-7

Cited by 18 publications

(18 citation statements)

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“…Similarly, analysis of the PBR revealed that the ‘higher’ primate MHC-E sequences are more closely related to the rodent Qa1 group than to any of the ‘lower’ primate sequences (Figure 4D). Thus, these findings indicate that the grey mouse lemur genome neither encodes a strict orthologue (with a one-to-one relationship) nor a functional homologue of MHC-E and confirm earlier data of our group that ‘higher’ and ‘lower’ primate MHC class I genes lack strict orthology [18].…”

Section: Resultssupporting

confidence: 90%

“…Interestingly, our screening of the mouse lemur BAC library for MHC class I genes also identified an unlinked genomic region that includes nine MHC class I genes. Complete sequencing of this region revealed six genes encoding functional MHC class I proteins, including putative alleles of the previously described classical class I genes of the mouse lemur, Mimu-W01 and Mimu-W04 [18] (Figure 1C). This class I gene cluster maps to another chromosome, the long arm of mouse lemur chromosome 26 (Figure 2), thus providing an additional example of a mammalian species where MHC class I and class II genes are not linked.…”

Section: Resultsmentioning

confidence: 92%

“…In addition to this unusual organisation of the grey mouse lemur MHC , a striking difference to ‘higher’ primates is the apparent absence of a strict HLA-E orthologue or functional homologue. As the BAC library was screened exhaustively and in the light of our genome-wide approach published earlier [18], it appears rather unlikely that MHC-E -like class I genes were not detected. Thus, the putative CD94/NKG2 ligands are expected among the sequenced MHC class I genes.…”

Section: Discussionmentioning

confidence: 99%

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A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

et al. 2009

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There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of non-polymorphic KLR in “higher” primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

et al. 2009

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“…In fact, all four residues of the Patr-AL motif are distributed among the MHC-E molecules of the simian primates (Figure S4). This observation, and knowledge that HLA-E is probably the oldest of the expressed MHC class I genes in simian primates (25, 26) raise the possibility that the FNSE motif first evolved at the MHC-E locus and was subsequently introduced into Patr-AL by recombination or gene conversion.…”

Section: Discussionmentioning

confidence: 98%

A Distinctive Cytoplasmic Tail Contributes to Low Surface Expression and Intracellular Retention of the Patr-AL MHC Class I Molecule

Goyos

Guethlein

Horowitz

et al. 2015

The Journal of Immunology

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Chimpanzees have orthologs of the six, fixed, functional human MHC class I genes. But in addition, the chimpanzee has a seventh functional gene, Patr-AL, which is not polymorphic but contributes substantially to population diversity by its presence on only 50% of MHC haplotypes. The ancestral AL gene emerged long before the separation of human and chimpanzee ancestors and then subsequently and specifically lost function during human evolution, but was maintained in chimpanzees. Patr-AL is an alloantigen that participates in negative and positive selection of the T-cell repertoire. The three-dimensional structure and the peptide-binding repertoire of Patr-AL and HLA-A*02 are surprisingly similar. In contrast, the expression of these two molecules is very different as shown using specific monoclonal and polyclonal antibodies made against Patr-AL. Peripheral blood cells and B cell lines express low levels of Patr-AL at the cell surface. Higher levels are seen for 221-cell transfectants expressing Patr-AL, but in these cells a large majority of Patr-AL molecules are retained in the early compartments of the secretory pathway: mainly the endoplasmic reticulum but also cis-Golgi. Replacing the cytoplasmic tail of Patr-AL with that of HLA-A*02 increased the cell-surface expression of Patr-AL substantially. Four substitutions distinguish the Patr-AL and HLA-A*02 cytoplasmic tails. Systematic mutagenesis showed that each substitution contributes changes in cell-surface expression. The combination of residues present in Patr-AL appears unique, but each individual residue is present in other primate MHC class I molecules, notably MHC-E, the most ancient of the functional human MHC class I molecules.

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“…All functional lemur MHC class I genes were translocated to a different chromosome and the MHC -containing chromosome harbors only MHC class I pseudogenes [38] . Orthologous relationships between strepsirrhine and catarrhine/platyrrhine MHC class I genes are not evident [39] . In the light of the polymorphic and diverse CD94/NKG2 receptors, one would anticipate several MHC-E -like genes in lemurs.…”

Section: Polymorphic Nk Cell Receptors Of Lemursmentioning

confidence: 99%

Major Histocompatibility Complex Class-I-Interacting Natural Killer Cell Receptors of Nonhuman Primates

Walter

2011

J Innate Immun

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Human natural killer (NK) cell receptors are known to be highly polymorphic, to show complex genetics and to be associated with susceptibility to a variety of immunological diseases. Nonhuman primates are used as important models of these diseases, yet the knowledge of nonhuman primate NK cell receptors and ligands is not as advanced as in humans. Recently published data indicated that diversity and polymorphism of NK cell receptors are similar between nonhuman primates and humans. Comparative genomics revealed instructive insights into the evolution and function of primate NK cell receptor genes and contributed to the understanding of how present-day NK cell receptors and their ligands have evolved. Here, I review the current knowledge of nonhuman primate NK cell receptors that interact with major histocompatibility complex class I proteins.

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Characterization and Phylogenetic Relationship of Prosimian MHC Class I Genes

Cited by 18 publications

References 0 publications

A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

A Distinctive Cytoplasmic Tail Contributes to Low Surface Expression and Intracellular Retention of the Patr-AL MHC Class I Molecule

Major Histocompatibility Complex Class-I-Interacting Natural Killer Cell Receptors of Nonhuman Primates

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