Major histocompatibility complex genotyping with massively parallel pyrosequencing

Wiseman, Roger W.; Karl, Julie A.; Bimber, Benjamin N.; O’Leary, Claire E.; Lank, Simon M.; Tuscher, Jennifer J.; Detmer, Ann; Bouffard, Pascal; Levenkova, Natalya; Turcotte, Cynthia; Szekeres, Edward S.; Wright, Chris; Harkins, Timothy T.; O’Connor, David H.

doi:10.1038/nm.2038

Cited by 134 publications

(161 citation statements)

References 26 publications

(35 reference statements)

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“…Notably, origin-specific allelic variation of MHC class I is also observed between these three populations [18,54,55]. Therefore, Eur.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, origin-specific allelic variation of MHC class I is also observed between these three populations [18,54,55]. Therefore, it may be relevant to functionally examine whether these originspecific MHC and KIR alleles encode for receptor-ligand pairs.…”

Section: Discussionmentioning

confidence: 99%

“…RNA was isolated from PBMCs with Trizol reagent (Invitrogen, Paisley, Scotland), and first-strand cDNA synthesis was performed with a poly- (18)dT primer according to the standard protocol (Fermentas, St. Leon-Rot, Germany).…”

Section: Isolation Of Genomic Dna and Cdnamentioning

confidence: 99%

“…In both species, the MHC has evolved in its own manner; functionally, however, these molecules behave in the same way. For instance, one haplotype can comprise multiple Mamu-A and -B genes, which can be subdivided, however, into high-level (majors) and low-level (minors) transcribed genes [18]. As a consequence, the end result may resemble the situation in humans.…”

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confidence: 99%

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The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

et al. 2011

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NK cells are essential in shaping immune responses and play an important role during pregnancy and in controlling infections. Killer cell immunoglobulin-like receptors (KIRs) educate the NK cell and determine its state of activation. Our goal was to determine how the KIR repertoire of the rhesus macaque (Macaca mulatta) has been shaped during evolution. The presence or absence of 22 KIR gene groups was determined in 378 animals. Some unexpected observations were made in an outbred colony comprising animals of different origins. For instance, the KIR region appears to be highly plastic, and an unprecedented number of genotypes and haplotypes was observed. In contrast to humans, there is no distinction between group A and B haplotypes in the rhesus macaque, suggesting that different selective forces may be operative. Moreover, specific genes appear to be either present or absent in animals of different geographic origins. This extreme plasticity may have been propelled by co-evolution with the rhesus macaque MHC class I region, which shows signatures of expansion. The mosaic-like complexity of KIR genotypes as observed at the population level may represent an effective strategy for surviving epidemic infections. [3] but they are also involved with the vascularisation process during placentation, and thus contribute to reproductive success [4]. The education and activation state of the NK-cell is determined by the interactions of its receptors with their cognate ligands [5]. It is the shift in equilibrium of inhibitory and activating receptor signaling that ultimately leads to NK-cell activation in the form of cytokine production, cytotoxicity, or priming of the adaptive immune system [6].Killer cell immunoglobulin-like receptors (KIRs) may influence this balance through interactions with their ligands, the MHC molecules, which are called human leukocyte antigens 2719(HLA) in humans. Since both the HLA system and the KIR gene complex are characterized by variation in locus content, and segregate independent of each other, the potential array of interactions can vary considerably between individuals. Understanding the evolution and complexity of these receptor systems has broad medical relevance, since particular combinations of KIR and HLA alleles are associated with the outcome of viral infection, relapse of leukemia after transplantation, susceptibility to autoimmune disease, and successful pregnancy [7][8][9][10]. Because of its close evolutionary relationship to humans, and evidenced by similar immunological responses, the rhesus macaque (Macaca mulatta) is an important animal model to study the onset, progression, and outcome of infectious diseases, experimentally induced autoimmunity, and transplantation [11][12][13]. Moreover, certain human pathogens or their simiantrophic family members have adapted to primates as their natural host, and may show a host-specific pathology. Since in an experimental setting the onset of disease or the actual challenge with a pathogen can be controlled, it is possible to stu...

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“…Notably, origin-specific allelic variation of MHC class I is also observed between these three populations [18,54,55]. Therefore, Eur.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Genomic Dna and Cdnamentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

et al. 2011

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“…The resulting sequencing data were binned by multiplex identifier, and sequence reads from each animal were assembled into unidirectional contigs having 100% identity using a custom genotyping analysis work flow (LabKey, USA). The number of sequence reads comprising each unidirectional contig was enumerated, and the resulting consensus sequences were mapped against an in-house database containing known pig-tailed MHC-I allele sequences using the BLASTn program (33)(34)(35). Putative Mane-A and Mane-B haplotypes were inferred by identifying combinations of shared alleles between animals as described previously for rhesus macaques (35).…”

Section: Methodsmentioning

confidence: 99%

Linking Pig-Tailed Macaque Major Histocompatibility Complex Class I Haplotypes and Cytotoxic T Lymphocyte Escape Mutations in Simian Immunodeficiency Virus Infection

Gooneratne

Alinejad‐Rokny

Ebrahimi

et al. 2014

J Virol

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The influence of major histocompatibility complex class I (MHC-I) alleles on human immunodeficiency virus (HIV) diversity in humans has been well characterized at the population level. MHC-I alleles likely affect viral diversity in the simian immunodeficiency virus (SIV)-infected pig-tailed macaque (Macaca nemestrina) model, but this is poorly characterized. We studied the evolution of SIV in pig-tailed macaques with a range of MHC-I haplotypes. SIV mac251 genomes were amplified from the plasma of 44 pig-tailed macaques infected with SIV mac251 at 4 to 10 months after infection and characterized by Illumina deep sequencing. MHC-I typing was performed on cellular RNA using Roche/454 pyrosequencing. MHC-I haplotypes and viral sequence polymorphisms at both individual mutations and groups of mutations spanning 10-amino-acid segments were linked using in-house bioinformatics pipelines, since cytotoxic T lymphocyte (CTL) escape can occur at different amino acids within the same epitope in different animals. The approach successfully identified 6 known CTL escape mutations within 3 Mane-A1*084-restricted epitopes. The approach also identified over 70 new SIV polymorphisms linked to a variety of MHC-I haplotypes. Using functional CD8 T cell assays, we confirmed that one of these associations, a Mane-B028 haplotype-linked mutation in Nef, corresponded to a CTL epitope. We also identified mutations associated with the Mane-B017 haplotype that were previously described to be CTL epitopes restricted by Mamu-B*017:01 in rhesus macaques. This detailed study of pig-tailed macaque MHC-I genetics and SIV polymorphisms will enable a refined level of analysis for future vaccine design and strategies for treatment of HIV infection. IMPORTANCECytotoxic T lymphocytes select for virus escape mutants of HIV and SIV, and this limits the effectiveness of vaccines and immunotherapies against these viruses. Patterns of immune escape variants are similar in HIV type 1-infected human subjects that share the same MHC-I genes, but this has not been studied for SIV infection of macaques. By studying SIV sequence diversity in 44 MHC-typed SIV-infected pigtail macaques, we defined over 70 sites within SIV where mutations were common in macaques sharing particular MHC-I genes. Further, pigtail macaques sharing nearly identical MHC-I genes with rhesus macaques responded to the same CTL epitope and forced immune escape. This allows many reagents developed to study rhesus macaques to also be used to study pigtail macaques. Overall, our study defines sites of immune escape in SIV in pigtailed macaques, and this enables a more refined level of analysis of future vaccine design and strategies for treatment of HIV infection.

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Large Animal Models of Transplantation

Anderson

Martin

Kirk

et al. 2014

Textbook of Organ Transplantation

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Major histocompatibility complex genotyping with massively parallel pyrosequencing

Cited by 134 publications

References 26 publications

The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

Linking Pig-Tailed Macaque Major Histocompatibility Complex Class I Haplotypes and Cytotoxic T Lymphocyte Escape Mutations in Simian Immunodeficiency Virus Infection

Large Animal Models of Transplantation

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