Genomic sequence encoding diversity segments of the pig TCR δ chain gene demonstrates productivity of highly diversified repertoire

Uenishi, Hirohide; Eguchi-Ogawa, Tomoko; Toki, Daisuke; Morozumi, Takeya; Tanaka-Matsuda, Maiko; Shinkai, Hiroki; Yamamoto, Ryûji; Takagaki, Yohtaroh

doi:10.1016/j.molimm.2008.11.010

Cited by 26 publications

(10 citation statements)

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“…Pig has at least 6 Dδ genes, while human and mouse have 3 and 2, respectively. The pig Dδ genes are frequently used in functional TCR δ transcripts with up to 4 concatenated domains [52]. Thus, the pig can generate a high diversity of TCR δ chain molecules to cope with antigens, which may be related to the fact that the percentage of γδ T cells in peripheral blood is much higher in pig than in human and mouse [17].…”

Section: Resultsmentioning

confidence: 99%

Structural and functional annotation of the porcine immunome

et al. 2013

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BackgroundThe domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.ResultsThe Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.ConclusionsThis extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig’s adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.

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Section: Resultsmentioning

confidence: 99%

Structural and functional annotation of the porcine immunome

et al. 2013

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“…To date, five and at least six TRDD genes have been demonstrated in bovine and pig TRD locus, respectively [ 14 , 26 ]. In contrast to a previous report [ 9 ] but consistent with human and pig (IMGT®, http://www.imgt.org ; [ 26 ]), four TRDJ genes are located upstream of the TRDC gene. Similarly to human and pig, at least 61 TRAJ genes lie in the genomic region between TRDC and TRAC (Fig.…”

Section: Resultsmentioning

confidence: 99%

Sheep (Ovis aries) T cell receptor alpha (TRA) and delta (TRD) genes and genomic organization of the TRA/TRD locus

et al. 2015

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BackgroundIn mammals, T cells develop along two discrete pathways characterized by expression of either the αβ or the γδ T cell receptors. Human and mouse display a low peripheral blood γδ T cell percentage ("γδ low species") while sheep, bovine and pig accounts for a high proportion of γδ T lymphocytes ("γδ high species"). While the T cell receptor alpha (TRA) and delta (TRD) genes and the genomic organization of the TRA/TRD locus has been determined in human and mouse, this information is still poorly known in artiodactyl species, such as sheep.ResultsThe analysis of the current Ovis aries whole genome assembly, Oar_v3.1, revealed that, as in the other mammalian species, the sheep TRD locus is nested within the TRA locus. In the most 5’ part the TRA/TRD locus contains TRAV genes which are intermingled with TRDV genes, then TRD genes which include seven TRDD, four TRDJ genes, one TRDC and a single TRDV gene with an inverted transcriptional orientation, and finally in the most 3’ part, the TRA locus is completed by 61 TRAJ genes and one TRAC gene.Comparative sequence and analysis and annotation led to the identification of 66 TRAV genes assigned to 34 TRAV subgroups and 25 TRDV genes belonging to the TRDV1 subgroup, while one gene was found for each TRDV2, TRDV3 and TRDV4 subgroups. Multiple duplication events within several TRAV subgroups have generated the sheep TRAV germline repertoire, which is substantially larger than the human one. A significant proportion of these TRAV gene duplications seems to have occurred simultaneously with the amplification of the TRDV1 subgroup genes. This dynamic of expansion has also generated novel multigene subgroups, which are species-specific. Ovis aries TRA and TRD genes identified in this study were assigned IMGT definitive or temporary names and were approved by the IMGT/WHO-IUIS nomenclature committee.The completeness of the genome assembly in the 3' part of the locus has allowed us to interpret rearranged CDR3 of cDNA from both TRA and TRD chain repertoires. The involvement of one up to four TRDD genes into a single transcript makes the potential sheep TRD chain much larger than any known TR chain repertoire.ConclusionsThe sheep genome, as the bovine genome, contains a large and diverse repertoire of TRA and TRD genes when compared to the “γδ T cell low” species genomes. The composition and length of the rearranged CDR3 in TRD V-delta domains influence the three-dimensional configuration of the antigen-combining site thus suggesting that in ruminants, γδ T cells play a more important and specific role in immune recognition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1790-z) contains supplementary material, which is available to authorized users.

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“…In swine, recent completion of the porcine genome is likely to stimulate a wave of research and publications that build on previous work to greatly expand our molecular and genetic understanding of porcine immunology, and provide a critical framework for new tool development (Dawson et al, 2013; Groenen et al, 2012; Haverson et al, 2001; Lunney et al, 1994; Saalmuller et al, 1998). Purified protein and antibody reagents are increasingly available to elucidate immune developmental and regulatory pathways in animal species, as are molecular tools and sequence data for characterization of humoral and cellular immune effector functions (Butler, 1998; Butler et al, 2006; Butler et al, 2001; Butler et al, 2009; Butler et al, 2004; Eguchi-Ogawa et al, 2009; Eguchi-Ogawa et al, 2012; Eguchi-Ogawa et al, 2010; Honma et al, 2003; Schwartz et al, 2012a, b; Sinkora et al, 2002; Uenishi et al, 2009). Methods for recombinant antibody expression and tetramers for antigen-specific T-cell responses in swine have been developed (Butler et al, 2013; Patch et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

Advances in swine immunology help move vaccine technology forward

Murtaugh

2014

Veterinary Immunology and Immunopathology

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In veterinary animal species, vaccines are the primary tool for disease prevention, a key tool for treatment of infection, and essential for helping maintain animal welfare and productivity. Traditional vaccine development by trial-and-error has achieved many successes. However, effective vaccines that provide solid cross-protective immunity with excellent safety are still needed for many diseases. The path to development of vaccines against difficult pathogens requires recognition of uniquely evolved immunological interactions of individual animal hosts and their specific pathogens. Here, general principles that currently guide veterinary immunology and vaccinology research are reviewed, with an emphasis on examples from swine. Advances in genomics and proteomics now provide the community with powerful tools for elucidation of regulatory and effector mechanisms of protective immunity that provide new opportunities for successful translation of immunological discoveries into safe and effective vaccines.

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Genomic sequence encoding diversity segments of the pig TCR δ chain gene demonstrates productivity of highly diversified repertoire

Cited by 26 publications

References 46 publications

Structural and functional annotation of the porcine immunome

Structural and functional annotation of the porcine immunome

Sheep (Ovis aries) T cell receptor alpha (TRA) and delta (TRD) genes and genomic organization of the TRA/TRD locus

Advances in swine immunology help move vaccine technology forward

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