scholarly journals Major histocompatibility complex haplotyping and long-amplicon allele discovery in cynomolgus macaques from Chinese breeding facilities

2016 ◽  
Author(s):  
Julie A. Karl ◽  
Michael E. Graham ◽  
Roger W. Wiseman ◽  
Katelyn E. Heimbruch ◽  
Samantha M. Gieger ◽  
...  

ABSTRACTVery little is currently known about the major histocompatibility complex (MHC) region of cynomolgus macaques (Macaca fascicularis; Mafa) from Chinese breeding centers. We performed comprehensive MHC class I haplotype analysis of 100 cynomolgus macaques from two different centers, with animals from different reported original geographic origins (Vietnamese, Cambodian, and Cambodian/Indonesian mixed-origin). Many of the samples were of known relation to each other (sire, dam, and progeny sets), making it possible to characterize lineage-level haplotypes in these animals. We identified 52 Mafa-A and 74 Mafa-B haplotypes in this cohort, many of which were restricted to specific sample origins. We also characterized full-length MHC class I transcripts using Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) sequencing. This technology allows for complete read-through of unfragmented MHC class I transcripts (~1,100 bp in length), so no assembly is required to unambiguously resolve novel full-length sequences. Overall, we identified 313 total full-length transcripts in a subset of 72 cynomolgus macaques from these Chinese breeding facilities; 131 of these sequences were novel and an additional 116 extended existing short database sequences to span the complete open reading frame. This significantly expands the number of Mafa-A, Mafa-B, and Mafa-I full-length alleles in the official cynomolgus macaque MHC class I database. The PacBio technique described here represents a general method for full-length allele discovery and genotyping that can be extended to other complex immune loci such as MHC class II, killer immunoglobulin-like receptors, and Fc gamma receptors.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 963 ◽  
Author(s):  
Johannes M. Dijkstra ◽  
Unni Grimholt

This correspondence concerns a publication by Malmstrøm et al. in Nature Genetics in October 2016. Malmstrøm et al. made an important contribution to fish phylogeny research by using low-coverage genome sequencing for comparison of 66 teleost (modern bony) fish species, with 64 of those 66 belonging to the species-rich clade Neoteleostei, and with 27 of those 64 belonging to the order Gadiformes. For these 66 species, Malmstrøm et al. estimated numbers of genes belonging to the major histocompatibility complex (MHC) class I lineages U and Z and concluded that in teleost fish these combined numbers are positively associated with, and a driving factor of, the rates of establishment of new fish species (speciation rates). They also claimed that functional genes for the MHC class II system molecules MHC IIA, MHC IIB, CD4 and CD74 were lost in early Gadiformes. Our main criticisms are (1) that the authors did not provide sufficient evidence for presence or absence of intact functional MHC class I or MHC class II system genes, (2) that they did not discuss that an MHC subpopulation gene number alone is a very incomplete measure of MHC variance, and (3) that the MHC system is more likely to reduce speciation rates than to enhance them. We conclude that their new model of MHC class I evolution, reflected in their title “Evolution of the immune system influences speciation rates in teleost fish”, is unsubstantiated. In addition, we explain that their “pinpointing” of the functional loss of the MHC class II system and all the important MHC class II system genes to the onset of Gadiformes is preliminary, because they did not sufficiently investigate the species at the clade border.



2017 ◽  
Vol 70 (6) ◽  
pp. 381-399 ◽  
Author(s):  
Matthew R. Semler ◽  
Roger W. Wiseman ◽  
Julie A. Karl ◽  
Michael E. Graham ◽  
Samantha M. Gieger ◽  
...  


2007 ◽  
Vol 59 (4) ◽  
pp. 305-321 ◽  
Author(s):  
Johannes Martinus Dijkstra ◽  
Takayuki Katagiri ◽  
Kazuyoshi Hosomichi ◽  
Kazuyo Yanagiya ◽  
Hidetoshi Inoko ◽  
...  


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 963
Author(s):  
Johannes M. Dijkstra ◽  
Unni Grimholt

This correspondence concerns a publication by Malmstrøm et al. in Nature Genetics in October 2016. Malmstrøm et al. made an important contribution to fish phylogeny research by using low-coverage genome sequencing for comparison of 66 teleost (modern bony) fish species, with 64 of those 66 belonging to the species-rich clade Neoteleostei, and with 27 of those 64 belonging to the order Gadiformes. For these 66 species, Malmstrøm et al. estimated numbers of genes belonging to the major histocompatibility complex (MHC) class I lineages U and Z and concluded that in teleost fish these combined numbers are positively associated with, and a driving factor of, the rates of establishment of new fish species (speciation rates). They also claimed that functional genes for the MHC class II system molecules MHC IIA, MHC IIB, CD4 and CD74 were lost in early Gadiformes. Our main criticisms are (1) that the authors did not provide sufficient evidence for presence or absence of intact functional MHC class I or MHC class II system genes, (2) that they did not discuss that an MHC subpopulation gene number alone is a very incomplete measure of MHC variance, and (3) that the MHC system is more likely to reduce speciation rates than to enhance them. Furthermore, their use of the Ornstein-Uhlenbeck model is a typical example of overly naïve use of that model system. In short, we conclude that their new model of MHC class I evolution, reflected in their title “Evolution of the immune system influences speciation rates in teleost fish”, is unsubstantiated, and that their “pinpointing” of the functional loss of the MHC class II system and all the important MHC class II system genes to the onset of Gadiformes is preliminary, because they did not sufficiently investigate the species at the clade border.



2012 ◽  
Vol 279 (1746) ◽  
pp. 4457-4463 ◽  
Author(s):  
Maria Strandh ◽  
Helena Westerdahl ◽  
Mikael Pontarp ◽  
Björn Canbäck ◽  
Marie-Pierre Dubois ◽  
...  

Mate choice for major histocompatibility complex (MHC) compatibility has been found in several taxa, although rarely in birds. MHC is a crucial component in adaptive immunity and by choosing an MHC-dissimilar partner, heterozygosity and potentially broad pathogen resistance is maximized in the offspring. The MHC genotype influences odour cues and preferences in mammals and fish and hence olfactory-based mate choice can occur. We tested whether blue petrels, Halobaena caerulea , choose partners based on MHC compatibility. This bird is long-lived, monogamous and can discriminate between individual odours using olfaction, which makes it exceptionally well suited for this analysis. We screened MHC class I and II B alleles in blue petrels using 454-pyrosequencing and quantified the phylogenetic, functional and allele-sharing similarity between individuals. Partners were functionally more dissimilar at the MHC class II B loci than expected from random mating ( p = 0.033), whereas there was no such difference at the MHC class I loci. Phylogenetic and non-sequence-based MHC allele-sharing measures detected no MHC dissimilarity between partners for either MHC class I or II B. Our study provides evidence of mate choice for MHC compatibility in a bird with a high dependency on odour cues, suggesting that MHC odour-mediated mate choice occurs in birds.



Author(s):  
Cecilia G. Shortreed ◽  
Roger W. Wiseman ◽  
Julie A. Karl ◽  
Hailey E. Bussan ◽  
David A. Baker ◽  
...  

AbstractMany medical advancements – including improvements to anti-rejection therapies in transplantation and vaccine development – rely on pre-clinical studies conducted in cynomolgus macaques (Macaca fascicularis). Major histocompatibility complex (MHC) class I and class II genes of cynomolgus macaques are orthologous to human leukocyte antigen complex (HLA) class I and class II genes, respectively. Both encode cell-surface proteins involved in cell recognition and rejection of non-host tissues. MHC class I and class II genes are highly polymorphic, so comprehensive genotyping requires the development of complete databases of allelic variants. Our group used PacBio circular consensus sequencing of full-length cDNA amplicons to characterize MHC class I and class II transcript sequences for a cohort of 295 Indonesian cynomolgus macaques (ICM) in a large, pedigreed breeding colony. These studies allowed us to expand the existing database of Macaca fascicularis (Mafa) alleles by identifying an additional 141 MHC class I and 61 class II transcript sequences. In addition, we defined co-segregating combinations of allelic variants as regional haplotypes for 70 Mafa-A, 78 Mafa-B and 45 Mafa-DRB gene clusters. Finally, we defined class I and class II transcripts that are associated with 100 extended MHC haplotypes in this breeding colony by combining our genotyping analyses with short tandem repeat (STR) patterns across the MHC region. Our sequencing analyses and haplotype definitions improve the utility of these ICM for transplantation studies as well as infectious disease and vaccine research.



2002 ◽  
Vol 76 (16) ◽  
pp. 7942-7948 ◽  
Author(s):  
Karin E. Peterson ◽  
Ingunn Stromnes ◽  
Ron Messer ◽  
Kim Hasenkrug ◽  
Bruce Chesebro

ABSTRACT CD4+ Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8+ T-cell responses. However, in the present study with Friend murine retrovirus (FV), the reverse was also found to be true. In the absence of a responder H-2b allele at major histocompatibility complex (MHC) class II loci, a single H-2Db MHC class I allele was sufficient for the development of a CD4+ Th1 response to FV. This effect of H-2Db on CD4+ T-cell responses was dependent on CD8+ T cells, as demonstrated by depletion studies. A direct effect of CD8+ T-cell help in the development of CD4+ Th1 responses to FV was also shown in vaccine studies. Vaccination of nonresponder H-2a/a mice induced FV-specific responses of H-2Dd -restricted CD8+ cytotoxic T lymphocytes (CTL). Adoptive transfer of vaccine-primed CD8+ T cells to naive H-2a/a mice prior to infection resulted in the generation of FV-specific CD4+ Th1 responses. This novel helper effect of CD8+ T cells could be an important mechanism in the development of CD4+ Th1 responses following vaccinations that induce CD8+ CTL responses. The ability of MHC class I genes to facilitate CD4+ Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.



2017 ◽  
Vol 8 ◽  
Author(s):  
Marek Wieczorek ◽  
Esam T. Abualrous ◽  
Jana Sticht ◽  
Miguel Álvaro-Benito ◽  
Sebastian Stolzenberg ◽  
...  


1999 ◽  
Vol 189 (2) ◽  
pp. 371-380 ◽  
Author(s):  
Armelle Regnault ◽  
Danielle Lankar ◽  
Valérie Lacabanne ◽  
Ana Rodriguez ◽  
Clotilde Théry ◽  
...  

Dendritic cells (DCs) express several receptors for the Fc portion of immunoglobulin (Ig)G (FcγR), which mediate internalization of antigen–IgG complexes (immune complexes, ICs) and promote efficient major histocompatibility complex (MHC) class II–restricted antigen presentation. We now show that FcγRs have two additional specific attributes in murine DCs: the induction of DC maturation and the promotion of efficient MHC class I–restricted presentation of peptides from exogenous, IgG-complexed antigens. Both FcγR functions require the FcγR-associated γ chain. FcγR-mediated MHC class I–restricted antigen presentation is extremely sensitive and specific to immature DCs. It requires proteasomal degradation and is dependent on functional peptide transporter associated with antigen processing, TAP1-TAP2. By promoting DC maturation and presentation on both MHC class I and II molecules, ICs should efficiently sensitize DCs for priming of both CD4+ helper and CD8+ cytotoxic T lymphocytes in vivo.



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