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.
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.
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.
Summary
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.
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.
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.
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.
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.
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 (
) families. This high-resolution approach allowed the identification of novel
alleles, the extension of reported allele sequences, and the determination of human and macaque
haplotypes. In addition, multiple recombinant
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
cluster in humans and macaques, which eventually may aid in a better understanding and interpretation of
allele-associated diseases, as well as the immune response in transplantation and reproduction.
The killer-cell Ig-like receptors (KIR) form a multigene entity involved in modulating immune responses through interactions with MHC class I molecules. The complexity of the
cluster is reflected by, ...for instance, abundant levels of allelic polymorphism, gene copy number variation, and stochastic expression profiles. The current transcriptome study involving human and macaque families demonstrates that
family members are also subjected to differential levels of alternative splicing, and this seems to be gene dependent. Alternative splicing may result in the partial or complete skipping of exons, or the partial inclusion of introns, as documented at the transcription level. This post-transcriptional process can generate multiple isoforms from a single
gene, which diversifies the characteristics of the encoded proteins. For example, alternative splicing could modify ligand interactions, cellular localization, signaling properties, and the number of extracellular domains of the receptor. In humans, we observed abundant splicing for
, and to a lesser extent in the lineage III
genes. All experimentally documented splice events are substantiated by
splicing strength predictions. To a similar extent, alternative splicing is observed in rhesus macaques, a species that shares a close evolutionary relationship with humans. Splicing profiles of
and
displayed a great diversity, whereas
(lineage V) is consistently spliced to generate a homolog of human
(lineage I). The latter case represents an example of convergent evolution. Although just a single KIR splice event is shared between humans and macaques, the splicing mechanisms are similar, and the predicted consequences are comparable. In conclusion, alternative splicing adds an additional layer of complexity to the
gene system in primates, and results in a wide structural and functional variety of KIR receptors and its isoforms, which may play a role in health and disease.
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.
In different macaque species, the MHC
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
gene encodes a specialized MHC class I molecule, and is most likely transported to the cell surface only when suitable peptides become available.
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