RESUMO
The killer cell Ig-like receptors (KIR) modulate immune responses through interactions with MHC class I molecules. The KIR region in large cohorts of rhesus and cynomolgus macaque populations were characterized, and the experimental design enabled the definition of a considerable number of alleles (n = 576) and haplotypes, which are highly variable with regard to architecture. Although high levels of polymorphism were recorded, only a few alleles are shared between species and populations. The rapid evolution of allelic polymorphism, accumulated by point mutations, was further confirmed by the emergence of a novel KIR allele in a rhesus macaque family. In addition to allelic variation, abundant orthologous and species-specific KIR genes were identified, the latter of which are frequently generated by fusion events. The concerted action of both genetic mechanisms, in combination with differential selective pressures at the population level, resulted in the unparalleled rapid evolution of the KIR gene region in two closely related macaque species. The variation of the KIR gene repertoire at the species and population level might have an impact on the outcome of preclinical studies with macaque models.
Assuntos
Macaca fascicularis/genética , Macaca mulatta/genética , Receptores KIR/genética , Alelos , Animais , Evolução Molecular , Haplótipos/genética , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo Genético/genéticaRESUMO
The major histocompatibility complex (MHC) class I region of humans, chimpanzees (Pan troglodytes), and bonobos (Pan paniscus) is highly similar, and orthologues of HLA-A, -B, and -C are present in both Pan species. Based on functional characteristics, the different HLA-A allotypes are classified into different supertypes. One of them, the HLA A03 supertype, is widely distributed among different human populations. All contemporary known chimpanzee and bonobo MHC class I A allotypes cluster genetically into one of the six HLA-A families, the HLA-A1/A3/A11/A30 family. We report here that the peptide-binding motif of the Patr-A*05:01 allotype, which is commonly present in a cohort of western African chimpanzees, has a strong preference for binding peptides with basic amino acids at the carboxyl terminus. This phenomenon is shared with the family members of the HLA A03 supertype. Based on the chemical similarities in the peptide-binding pocket, we inferred that the preference for binding peptides with basic amino acids at the carboxyl terminus is widely present among the human, chimpanzee, and bonobo MHC-A allotypes. Subsequent in silico peptide-binding predictions illustrated that these allotypes have the capacity to target conserved parts of the proteome of human immunodeficiency virus type 1 (HIV-1) and the simian immunodeficiency virus SIVcpz.IMPORTANCE Most experimentally infected chimpanzees seem to control an HIV-1 infection and are therefore considered to be relatively resistant to developing AIDS. Contemporary free-ranging chimpanzees may carry SIVcpz, and there is evidence for AIDS-like symptoms in these free-ranging animals, whereas SIV infections in bonobos appear to be absent. In humans, the natural control of an HIV-1 infection is strongly associated with the presence of particular HLA class I allotypes. The ancestor of the contemporary living chimpanzees and bonobos survived a selective sweep targeting the MHC class I repertoire. We have put forward a hypothesis that this may have been caused by an ancestral retroviral infection similar to SIVcpz. Characterization of the relevant MHC allotypes may contribute to understanding the shaping of their immune repertoire. The abundant presence of MHC-A allotypes that prefer peptides with basic amino acids at the C termini suggests that these molecules may contribute to the control of retroviral infections in humans, chimpanzees, and bonobos.
Assuntos
Genes MHC Classe I/imunologia , Antígeno HLA-A3/imunologia , Primatas/imunologia , Alelos , Sequência de Aminoácidos , Animais , HIV-1/imunologia , Antígeno HLA-A3/metabolismo , Antígenos de Histocompatibilidade , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Pan paniscus/imunologia , Pan troglodytes/imunologia , Peptídeos/metabolismo , Filogenia , Ligação Proteica/imunologia , Infecções por Retroviridae/imunologia , Vírus da Imunodeficiência Símia/imunologiaRESUMO
The Killer-cell Immunoglobulin-like Receptors (KIR) are encoded by a diverse group of genes, which are characterized by allelic polymorphism, gene duplications, and recombinations, which may generate recombinant entities. The number of reported macaque KIR sequences is steadily increasing, and these data illustrate a gene system that may match or exceed the complexity of the human KIR cluster. This report lists the names of quality controlled and annotated KIR genes/alleles with all the relevant references for two different macaque species: rhesus and cynomolgus macaques. Numerous recombinant KIR genes in these species necessitate a revision of some of the earlier-published nomenclature guidelines. In addition, this report summarizes the latest information on the Immuno Polymorphism Database (IPD)-NHKIR Database, which contains annotated KIR sequences from four non-human primate species.
Assuntos
Bases de Dados Factuais , Imunogenética , Macaca mulatta/genética , Polimorfismo Genético , Receptores KIR/genética , Receptores KIR/imunologia , Terminologia como Assunto , AnimaisRESUMO
The major histocompatibility complex (MHC) is central to the innate and adaptive immune responses of jawed vertebrates. Characteristic of the MHC are high gene density, gene copy number variation, and allelic polymorphism. Because apes and monkeys are the closest living relatives of humans, the MHCs of these non-human primates (NHP) are studied in depth in the context of evolution, biomedicine, and conservation biology. The Immuno Polymorphism Database (IPD)-MHC NHP Database (IPD-MHC NHP), which curates MHC data of great and small apes, as well as Old and New World monkeys, has been upgraded. The curators of the database are responsible for providing official designations for newly discovered alleles. This nomenclature report updates the 2012 report, and summarizes important nomenclature issues and relevant novel features of the IPD-MHC NHP Database.
Assuntos
Bases de Dados Genéticas , Complexo Principal de Histocompatibilidade/genética , Primatas/genética , Primatas/imunologia , Alelos , Animais , Cercopithecidae/genética , Hominidae/genética , Complexo Principal de Histocompatibilidade/fisiologia , Filogenia , Platirrinos/genética , Polimorfismo Genético , Terminologia como AssuntoRESUMO
The original version of this article contained a spelling error in the Acknowledgments regarding the name of the funding organisation supporting GM and JAH. UKRI-BBSCR should have been UKRI-BBSRC, as is now indicated correctly below.
RESUMO
The killer-cell Ig-like receptors (KIRs) play a central role in the immune recognition in infection, pregnancy, and transplantation through their interactions with MHC class I molecules. KIR genes display abundant copy number variation as well as high levels of polymorphism. As a result, it is challenging to characterize this structurally dynamic region. KIR haplotypes have been analyzed in different species using conventional characterization methods, such as Sanger sequencing and Roche/454 pyrosequencing. However, these methods are time-consuming and often failed to define complete haplotypes, or do not reach allele-level resolution. In addition, most analyses were performed on genomic DNA, and thus were lacking substantial information about transcription and its corresponding modifications. In this paper, we present a single-molecule real-time sequencing approach, using Pacific Biosciences Sequel platform to characterize the KIR transcriptomes in human and rhesus macaque (Macaca mulatta) families. This high-resolution approach allowed the identification of novel Mamu-KIR alleles, the extension of reported allele sequences, and the determination of human and macaque KIR haplotypes. In addition, multiple recombinant KIR genes were discovered, all located on contracted haplotypes, which were likely the result of chromosomal rearrangements. The relatively high number of contracted haplotypes discovered might be indicative of selection on small KIR repertoires and/or novel fusion gene products. This next-generation method provides an improved high-resolution characterization of the KIR cluster in humans and macaques, which eventually may aid in a better understanding and interpretation of KIR allele-associated diseases, as well as the immune response in transplantation and reproduction.
Assuntos
Haplótipos/genética , Receptores KIR/genética , Transcriptoma/genética , Alelos , Animais , Variações do Número de Cópias de DNA/genética , Rearranjo Gênico/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Macaca mulatta , Polimorfismo Genético/genéticaRESUMO
Chimpanzees have been used for some time as an animal model in research on immune-related diseases in humans. The major histocompatibility complex (MHC) region of the chimpanzee has also been the subject of studies in which the attention was mainly on the class I genes. Although full-length sequence information is available on the DRB region genes, such detailed information is lacking for the other class II genes and, if present, is based mainly on exon 2 sequences. In the present study, full-length sequencing was performed on DQ, DP, and DRA genes in a cohort of 67 pedigreed animals, thereby allowing a thorough analysis of the MHC class II repertoire. The results demonstrate that the number of MHC class II lineages and alleles is relatively low, whereas haplotype diversity (combination of genes/alleles on a chromosome) seems to have been maximised by crossing-over processes.
Assuntos
Genes MHC da Classe II , Haplótipos , Pan troglodytes/genética , Alelos , Animais , Variação Genética , Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Pan troglodytes/imunologiaRESUMO
In different macaque species, the MHC A2*05 gene is present in abundance, and its gene products are characterized by low cell-surface expression and a highly conserved peptide-binding cleft. We have characterized the peptide-binding motif of Mamu-A2*05:01, and elucidated the binding capacity for virus-derived peptides. The macaque A2*05 allotype prefers the basic amino acid arginine at the second position of the peptide, and hydrophobic and polar amino acids at the C-terminal end. These preferences are shared with HLA-B*27 and Mamu-B*008, molecules shown to be involved in elite control in human HIV type 1 and macaque SIV infections, respectively. In contrast, however, Mamu-A2*05 preferentially binds 8-mer peptides. Retention in the endoplasmic reticulum seems to be the cause of the lower cell-surface expression. Subsequent peptide-binding studies have illustrated that Mamu-A2*05:01 is able to bind SIV-epitopes known to evoke a strong CD8+ T cell response in the context of the Mamu-B*008 allotype in SIV-infected rhesus macaques. Thus, the macaque A2*05 gene encodes a specialized MHC class I molecule, and is most likely transported to the cell surface only when suitable peptides become available.
Assuntos
Epitopos de Linfócito T/metabolismo , Infecções por HIV/imunologia , HIV/fisiologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Linfócitos T Citotóxicos/imunologia , Animais , Apresentação de Antígeno , Linhagem Celular , Epitopos de Linfócito T/genética , Predisposição Genética para Doença , Antígenos HIV/metabolismo , Infecções por HIV/genética , Antígeno HLA-B27/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Imunidade Celular , Macaca , Peptídeos/metabolismo , Ligação Proteica , Síndrome de Imunodeficiência Adquirida dos Símios/genética , Carga Viral , Replicação ViralRESUMO
Researchers dealing with the human leukocyte antigen (HLA) class I and killer immunoglobulin receptor (KIR) multi-gene families in humans are often wary of the complex and seemingly different situation that is encountered regarding these gene families in Old World monkeys. For the sake of comparison, the well-defined and thoroughly studied situation in humans has been taken as a reference. In macaques, both the major histocompatibility complex class I and KIR gene families are plastic entities that have experienced various rounds of expansion, contraction, and subsequent recombination processes. As a consequence, haplotypes in macaques display substantial diversity with regard to gene copy number variation. Additionally, for both multi-gene families, differential levels of polymorphism (allelic variation), and expression are observed as well. A comparative genetic approach has allowed us to answer questions related to ancestry, to shed light on unique adaptations of the species' immune system, and to provide insights into the genetic events and selective pressures that have shaped the range of these gene families.
Assuntos
Variação Genética/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Macaca mulatta/imunologia , Receptores KIR/imunologia , Animais , Variações do Número de Cópias de DNA/genética , Variações do Número de Cópias de DNA/imunologia , Evolução Molecular , Variação Genética/genética , Haplótipos , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Macaca mulatta/genética , Família Multigênica/genética , Família Multigênica/imunologia , Receptores KIR/genéticaRESUMO
The authors regret that an error was present in the Fig. 5 of the above article; some digits in the DRB allele-designations in Fig. 5 have been lost, and are incorrectly presented by only two digits. The correct allele-designations should have been four (or six) digits. The correct Figure is now presented correctly.
RESUMO
The IPD-MHC Database is the official repository for non-human MHC sequences, overseen and supported by the Comparative MHC Nomenclature Committee, providing access to curated MHC data and associated analysis tools. To address the increasing amount and complexity of data being submitted, an entirely upgraded version of the IPD-MHC Database was recently released to maintain IPD-MHC as the central platform for the comparison of curated MHC data. As a consequence, a new level of nomenclature standardisation is required between the different species to enable data submission and to allow the unambiguous inter- and intra-species comparison of alleles. However, any changes must retain the flexibility demanded by the unique biology of different taxonomic groups. Here, we describe the rationale for a standardised nomenclature system and summarise the changes that have been driven by the requirements of implementing the IPD-MHC database. This modified nomenclature system is essential to maintain the current functionality of IPD-MHC and provide a scalable future-proof database organisation to fully exploit the bioinformatic tools used for analysis.
Assuntos
Bases de Dados Genéticas , Antígenos de Histocompatibilidade/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Alelos , Animais , Bovinos , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos de Histocompatibilidade/genética , Humanos , Complexo Principal de Histocompatibilidade/genética , Ovinos/imunologiaRESUMO
Common chimpanzees (Pan troglodytes) experienced a selective sweep, probably caused by a SIV-like virus, which targeted their MHC class I repertoire. Based on MHC class I intron 2 data analyses, this selective sweep took place about 2-3 million years ago. As a consequence, common chimpanzees have a skewed MHC class I repertoire that is enriched for allotypes that are able to recognise conserved regions of the SIV proteome. The bonobo (Pan paniscus) shared an ancestor with common chimpanzees approximately 1.5 to 2 million years ago. To investigate whether the signature of this selective sweep is also detectable in bonobos, the MHC class I gene repertoire of two bonobo panels comprising in total 29 animals was investigated by Sanger sequencing. We identified 14 Papa-A, 20 Papa-B and 11 Papa-C alleles, of which eight, five and eight alleles, respectively, have not been reported previously. Within this pool of MHC class I variation, we recovered only 2 Papa-A, 3 Papa-B and 6 Papa-C intron 2 sequences. As compared to humans, bonobos appear to have an even more diminished MHC class I intron 2 lineage repertoire than common chimpanzees. This supports the notion that the selective sweep may have predated the speciation of common chimpanzees and bonobos. The further reduction of the MHC class I intron 2 lineage repertoire observed in bonobos as compared to the common chimpanzee may be explained by a founding effect or other subsequent selective processes.
Assuntos
Especiação Genética , Antígenos de Histocompatibilidade Classe I/genética , Íntrons , Pan paniscus/genética , Pan troglodytes/genética , Filogenia , Alelos , Sequência de Aminoácidos , Animais , Feminino , Frequência do Gene , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos de Histocompatibilidade Classe I/classificação , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Masculino , Pan paniscus/classificação , Pan paniscus/imunologia , Pan troglodytes/classificação , Pan troglodytes/imunologia , Seleção Genética , Alinhamento de SequênciaRESUMO
The human major histocompatibility complex (MHC) region encodes three types of class II molecules designated HLA-DR, -DQ, and -DP. Both the HLA-DQ and -DP gene region comprise a duplicated tandem of A and B genes, whereas in macaques, only one set of genes is present per region. A substantial sequencing project on the DQ and DP genes in various macaque populations resulted in the detection of previously 304 unreported full-length alleles. Phylogenetic studies showed that humans and macaques share trans-species lineages for the DQA1 and DQB1 genes, whereas the DPA1 and DPB1 lineages in macaques appear to be species-specific. Amino acid variability plot analyses revealed that each of the four genes displays more allelic variation in macaques than is encountered in humans. Moreover, the numbers of different amino acids at certain positions in the encoded proteins are higher than in humans. This phenomenon is remarkably prominent at the contact positions of the peptide-binding sites of the deduced macaque DPß-chains. These differences in the MHC class II DP regions of macaques and humans suggest separate evolutionary mechanisms in the generation of diversity.
Assuntos
Evolução Biológica , Variação Genética/genética , Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Macaca mulatta/classificação , Macaca mulatta/genética , Alelos , Animais , Frequência do Gene , Haplótipos , Humanos , FilogeniaRESUMO
A panel of 15 carefully selected microsatellites (short tandem repeats, STRs) has allowed us to study segregation and haplotype stability in various macaque species. The STRs span the major histocompatibility complex (MHC) region and map in more detail from the centromeric part of the Mhc-A to the DR region. Two large panels of Indian rhesus and Indonesian/Indochinese cynomolgus macaques have been subjected to pedigree analysis, allowing the definition of 161 and 36 different haplotypes and the physical mapping of 10 and 5 recombination sites, respectively. Although most recombination sites within the studied section of the Indian rhesus monkey MHC are situated between the Mhc-A and Mhc-B regions, the resulting recombination rate for this genomic segment is low and similar to that in humans. In contrast, in Indonesian/Indochinese macaques, two recombination sites, which appear to be absent in rhesus macaques, map between the class III and II regions. As a result, the mean recombination frequency of the core MHC, Mhc-A to class II, is higher in Indonesian/Indochinese cynomolgus than in Indian rhesus macaques, but as such is comparable to that in humans. The present communication demonstrates that the dynamics of recombination 'hot/cold spots' in the MHC, as well as their frequencies, may differ substantially between highly related macaque species.
Assuntos
Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Haplótipos/genética , Macaca fascicularis/genética , Macaca mulatta/genética , Repetições de Microssatélites/genética , Recombinação Genética/genética , Animais , DNA/genética , Frequência do Gene , Reação em Cadeia da PolimeraseRESUMO
In humans, the classical antigen presentation function of major histocompatibility complex (MHC) class I molecules is controlled by the human leukocyte antigen HLA -A, HLA-B and HLA-C loci. A similar observation has been made for great apes and Old World monkey species. In contrast, a New World monkey species such as the cotton-top tamarin (Saguinus oedipus) appears to employ the G locus for its classical antigen presentation function. At present, little is known about the classical MHC class I repertoire of the common marmoset (Callithrix jacchus), another New World monkey that is widely used in biomedical research. In the present population study, no evidence has been found for abundant transcription of classical I class genes. However, in each common marmoset, four to seven different G-like alleles were detected, suggesting that the ancestral locus has been subject to expansion. Segregation studies provided evidence for at least two G-like genes present per haplotype, which are transcribed by a variety of cell types. The alleles of these Caja-G genes cluster in separate lineages, suggesting that the loci diversified considerably after duplication. Phylogenetic analyses of the introns confirm that the Caja-G loci cluster in the vicinity of HLA-G, indicating that both genes shared an ancestor. In contrast to HLA-G, Caja-G shows considerable polymorphism at the peptide-binding sites. This observation, together with the lack of detectable transcripts of A and B-like genes, indicates that Caja-G genes have taken over the function of classical class I genes. These data highlight the extreme plasticity of the MHC class I gene system.
Assuntos
Callithrix/genética , Genes MHC Classe I , Antígenos HLA-G , Alelos , Animais , Callithrix/imunologia , Evolução Molecular , Antígenos HLA-G/genética , Antígenos HLA-G/imunologia , Humanos , Filogenia , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
Indian and Chinese rhesus macaques are often used in biomedical research. Genetic analyses of the major histocompatibility class I region have revealed that these macaques display a substantial level of polymorphism at Mamu-A and Mamu-B loci, which have been subject to duplication. Only a few Mamu class I allotypes are characterised for their peptide-binding motifs, although more information of this nature would contribute to a better interpretation of T cell-mediated immune responses. Here, we present the results of the characterisation of the functional properties of Mamu-B*037:01, an allotype commonly encountered in rhesus macaques of Indian and Chinese origin. Mamu-B*037:01 is seen to have a strong preference for acidic amino acids at the third residue, and for arginine, lysine, and tyrosine at the carboxyl terminus. This peptide-binding motif is not described in the human population.
Assuntos
Motivos de Aminoácidos/genética , Genes MHC da Classe II/genética , Macaca mulatta/genética , Peptídeos/genética , Animais , Povo Asiático , Genes MHC da Classe II/imunologia , Humanos , Índia , Macaca mulatta/imunologiaRESUMO
The Mamu-A, Mamu-B, and Mamu-DRB genes of the rhesus macaque show several levels of complexity such as allelic heterogeneity (polymorphism), copy number variation, differential segregation of genes/alleles present on a haplotype (diversity) and transcription level differences. A combination of techniques was implemented to screen a large panel of pedigreed Indian rhesus macaques (1,384 individuals representing the offspring of 137 founding animals) for haplotype diversity in an efficient and inexpensive manner. This approach allowed the definition of 140 haplotypes that display a relatively low degree of region variation as reflected by the presence of only 17 A, 18 B and 22 DRB types, respectively, exhibiting a global linkage disequilibrium comparable to that in humans. This finding contrasts with the situation observed in rhesus macaques from other geographic origins and in cynomolgus monkeys from Indonesia. In these latter populations, nearly every haplotype appears to be characterised by a unique A, B and DRB region. In the Indian population, however, a reshuffling of existing segments generated "new" haplotypes. Since the recombination frequency within the core MHC of the Indian rhesus macaques is relatively low, the various haplotypes were most probably produced by recombination events that accumulated over a long evolutionary time span. This idea is in accord with the notion that Indian rhesus macaques experienced a severe reduction in population during the Pleistocene due to a bottleneck caused by geographic changes. Thus, recombination-like processes appear to be a way to expand a diminished genetic repertoire in an isolated and relatively small founder population.
Assuntos
Variação Genética , Haplótipos , Macaca mulatta/genética , Complexo Principal de Histocompatibilidade/genética , Recombinação Genética , Animais , Linhagem Celular , Cromossomos de Mamíferos/genética , Evolução Molecular , Éxons , Feminino , Técnicas de Genotipagem , Índia , Desequilíbrio de Ligação , Masculino , Repetições de Microssatélites , Mianmar , LinhagemRESUMO
Cynomolgus macaques (Macaca fascicularis) are used widely in biomedical research, and the genetics of their MHC (Mhc-Mafa) has become the focus of considerable attention in recent years. The cohort of Indonesian pedigreed macaques that we present here was typed for Mafa-A, -B, and -DR, by sequencing, as described in earlier studies. Additionally, the DRB region of these animals was characterised by microsatellite analyses. In this study, full-length sequencing of Mafa-DPA/B and -DQA/B in these animals was performed. A total of 75 different alleles were observed; 22 of which have not previously been reported, plus 18 extended exon 2 alleles that were already known. Furthermore, two microsatellites, D6S2854 and D6S2859, were used to characterise the complex Mafa-A region. Sequencing and segregation analyses revealed that the length patterns of these microsatellites are unique for each Mafa-A haplotype. In this work, we present a pedigreed colony of approximately 120 cynomolgus macaques; all of which are typed for the most significant polymorphic MHC class I and class II markers. Offspring of these pedigreed animals are easily characterised for their MHC by microsatellite analyses on the Mafa-A and -DRB regions, which makes the cumbersome sequencing analyses redundant.
Assuntos
Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Haplótipos/genética , Macaca fascicularis/genética , Alelos , Animais , Feminino , Masculino , Repetições de Microssatélites , LinhagemRESUMO
The DR region of particular primate species may display allelic polymorphism and gene copy number variation (region configuration polymorphism). The sum of these distinct types of polymorphism is defined as complexity. To date, however, the DR region of cynomolgus macaques (Macaca fascicularis) has been poorly defined. Transcriptome analysis of a pedigreed colony, comprising animals from Indonesia and Indochina, revealed a total of 15 Mafa-DRA and 57 DRB alleles, specifying 28 different region configurations. The DRA alleles can be divided into two distinct lineages. One lineage is polymorphic, but the majority of the amino acid replacements map to the leader peptide. The second lineage is at best oligomorphic, and segregates with one specific Mafa-DRB allele. The number of Mafa-DRB genes ranges from two to five per haplotype. Due to the presence of pseudogenes, however, each haplotype encodes only one to three bona fide DRB transcripts. Depending on the region configuration in which the Mafa-DRB gene is embedded, identical alleles may display differential transcription levels. Region configurations appear to have been generated by recombination-like events. When genes or gene segments are relocated, it seems plausible that they may be placed in the context of distinct transcription control elements. As such, DRB region-related transcription level differences may add an extra layer of polymorphism to this section of the adaptive immune system.
Assuntos
Antígenos HLA-DR/genética , Macaca fascicularis/genética , Transcriptoma , Animais , Linhagem Celular , Feminino , Haplótipos , Masculino , Linhagem , Polimorfismo GenéticoRESUMO
The major histocompatibility complex (MHC) plays a central role in the adaptive immune response. The MHC region is characterised by a high gene density, and most of these genes display considerable polymorphism. Next to humans, non-human primates (NHP) are well studied for their MHC. The present nomenclature report provides the scientific community with the latest nomenclature guidelines/rules and current implemented nomenclature revisions for Great Ape, Old and New World monkey species. All the currently published MHC data for the different Great Ape, Old and New World monkey species are archived at the Immuno Polymorphism Database (IPD)-MHC NHP database. The curators of the IPD-MHC NHP database are, in addition, responsible for providing official designations for newly detected polymorphisms.