Swine Leukocyte Antigen Diversity in Canadian Specific Pathogen-Free Yorkshire and Landrace Pigs

Gao, Caixia; Quan, Jinqiang; Jiang, Xinjie; Li, Changwen; Lu, Xiaoye; Chen, Hongyan

doi:10.3389/fimmu.2017.00282

Cited by 20 publications

(34 citation statements)

References 41 publications

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“…The SLA-1 gene has the highest expression level ( Tennant et al, 2007 ), implying that SLA-1 molecules might play a dominant role in the immune process, including presentation of CTL epitopes. Sixty-nine SLA-1 alleles, identified in various pig breeds and cell lines ( Smith et al, 2005 ; Lee et al, 2005 , 2008 ; Ho et al, 2006 , 2009 , 2010 ; Gao et al, 2014 , 2017 ), have been deposited in the IPD-MHC SLA sequence database to date, and this number is increasing as more efficient SLA-typing techniques are employed and more experimental pig breeds are developed worldwide. Polymorphism of SLA class I molecules is concentrated in the region of the PBG, and determines the distinct structure of the PBG.…”

Section: Discussionmentioning

confidence: 99%

Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro

Gao

Quan

et al. 2017

Front. Microbiol.

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Swine leukocyte antigen (SLA) class I molecules play a crucial role in generating specific cellular immune responses against viruses and other intracellular pathogens. They mainly bind and present antigens of intracellular origin to circulating MHC I-restricted cytotoxic T lymphocytes (CTLs). Binding of an appropriate epitope to an SLA class I molecule is the single most selective event in antigen presentation and the first step in the killing of infected cells by CD8+ CTLs. Moreover, the antigen epitopes are strictly restricted to specific SLA molecules. In this study, we constructed SLA class I complexes in vitro comprising viral epitope peptides, the extracellular region of the SLA-1 molecules, and β2-microglobulin (β2m) using splicing overlap extension polymerase chain reaction (SOE-PCR). The protein complexes were induced and expressed in an Escherichia coli prokaryotic expression system and subsequently purified and refolded. Specific binding of seven SLA-1 proteins to one classical swine fever virus (CSFV) and four porcine reproductive and respiratory syndrome virus (PRRSV) epitope peptides was detected by enzyme-linked immunosorbent assay (ELISA)-based method. The SLA-1∗13:01, SLA-1∗11:10, and SLA-1∗11:01:02 proteins were able to bind specifically to different CTL epitopes of CSFV and PRRSV and the MHC restrictions of the five epitopes were identified. The fixed combination of Asn151Val152 residues was identified as the potentially key amino acid residues influencing the binding of viral several CTL epitope peptides to SLA-1∗13:01 and SLA-1∗04:01:01 proteins. The more flexible pocket E in the SLA-1∗13:01 protein might have fewer steric limitations and therefore be able to accommodate more residues of viral CTL epitope peptides, and may thus play a critical biochemical role in determining the peptide-binding motif of SLA-1∗13:01. Characterization of the binding specificity of peptides to SLA class I molecules provides an important basis for epitope studies of infectious diseases in swine, and for the rational development of novel porcine vaccines, as well as for detailed studies of CTL responses in pigs used as animal models.

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Section: Discussionmentioning

confidence: 99%

Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro

Gao

Quan

et al. 2017

Front. Microbiol.

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“…We identified 123 cases of SLA-1 duplication-bearing typing results from the typing of 307 samples, and they were classified into 9 groups either belonging to previously reported haplotypes (Hp-2, 19, 20, 28, and 35) 28,30 or new SLA-1 haplotypes (SLA-1*21:02-23:02 11:03-21:01, 06:01-18:02 and 02:02-18:01 in which two linked SLA-1 loci are indicated by a dash '-') detected for the first time in this study ( Table 3, Table S1). SLA-1*02:02-18:01 was a new combination of previously reported alleles and the remainder were associated with new alleles ( Table 3).…”

Section: Identification Of New Sla-1 Duplication Haplotypesmentioning

confidence: 99%

SLA-1 Genetic Diversity in Pigs: Extensive Analysis of Copy Number Variation, Heterozygosity, Expression, and Breed Specificity

Choi

Lee

et al. 2020

Sci Rep

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Swine leukocyte antigens play indispensable roles in immune responses by recognizing a large numberof foreign antigens and thus, their genetic diversity plays a critical role in their functions. in this study, we developed a new high-resolution typing method for pig SLA-1 and successfully typed 307 individuals from diverse genetic backgrounds including 11 pure breeds, 1 cross bred, and 12 cell lines. We identified a total of 52 alleles including 18 novel alleles and 9 SLA-1 duplication haplotypes, including 4 new haplotypes. We observed significant differences in the distribution of SLA-1 alleles among the different pig breeds, including the breed specific alleles. SLA-1 duplication was observed in 33% of the chromosomes and was especially high in the biomedical model breeds such as SNU (100%) and NIH (76%) miniature pigs. Our analysis showed that SLA-1 duplication is associated with the increased level of SLA-1 mRnA expression in porcine cells compared to that of the single copy haplotype. therefore, we provide here the results of the most extensive genetic analysis on pig SLA-1. open Scientific RepoRtS | (2020) 10:743 | https://doi.org/10.1038/s41598-020-57712-5www.nature.com/scientificreports www.nature.com/scientificreports/ SLA-1, SLA-2, and SLA-3 are constitutively expressed classical MHC class I genes, but their expression may vary depending on the genetic differences. For example, SLA-1 is duplicated in the haplotypes Hp-2.0, Hp-8.0, Hp-11.0, Hp-12.0, Hp-19.0, Hp-20.0, and Hp-27.0 14,24-26 . In addition, SLA-1, 3, and 6 were not expressed in the haplotypes Hp-3.0, Hp-2.0, and Hp-5.0, respectively 24 . Recently, a method was reported to estimate the copy number of SLA-1 and to facilitate our understanding on the functional aspect of SLA-1 duplication 27 . The frequency of SLA-1 duplication could be abundant, but the detailed functional analysis is not been available.Therefore, we developed a genomic DNA based high resolution SLA-1 typing method with high accuracy regardless of CNVs and present the extensive analysis results of SLA-1 diversity including new alleles and haplotypes, and allelic distribution among different breeds. We also analyzed the level of SLA-1 expression in pig cells according to their copy numbers which could affect MHC class I-specific immune responses. The information presented in this study should contribute to improving our understanding on the genetic polymorphisms of SLA-1 in diverse pig breeds. ResultsDetermination of the SLA-1 specific region. To develop a genomic DNA-based typing method of SLA-1, the determination of conserved locus specific region to design SLA-1 specific primers is required. We previously reported the locus specific nucleotide sequence variations at the downstream promoter region from six classical SLA class I-related genes including . Here, we extended the results by incorporating genomic sequences from additional cloning and sequence analysis. As a result, we identified a SLA-1 specific motif between the TATA box and the CAP site in the 5ʹ UTR and designe...

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“…As pigs are largely outbred compared to rodents, fully immunocompetent porcine models display a high MHC class I allelic diversity with the number of known alleles continuously expanding with improved typing methods and growing interest in swine for biomedical research. 174,175 In particular, the development of a Next Generation Sequencing-based SLA-typing approach has allowed a fast identification of expressed SLA class I molecules, 174 thereby allowing selection of MHC-matched animals to be used for instance in a vaccine protocol or other immunological assays.…”

Section: The Porcine Immune Systemmentioning

confidence: 99%

Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research

et al. 2018

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The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E’s, is encompassed by 3 distinct phases of elimination, equilibrium, and escape. Despite impressive results in the clinic, cancer immunotherapy still has room for improvement as many patients remain unresponsive to therapy. Moreover, many of the preclinical results obtained in the widely used mouse models of cancer are lost in translation to human patients. To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, using alternative animal models more closely related to humans is a promising approach. Here, we describe 2 of the major alternative model systems: canine (spontaneous) and porcine (experimental) cancer models. Although dogs display a high rate of spontaneous tumor formation, an increased number of genetically modified porcine models exist. We suggest that the optimal immuno-oncology model may depend on the stage of cancer immunoediting in question. In particular, the spontaneous canine tumor models provide a unique platform for evaluating therapies aimed at the escape phase of cancer, while genetically engineered swine allow for elucidation of tumor-immune cell interactions especially during the phases of elimination and equilibrium.

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Swine Leukocyte Antigen Diversity in Canadian Specific Pathogen-Free Yorkshire and Landrace Pigs

Cited by 20 publications

References 41 publications

Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro

Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro

SLA-1 Genetic Diversity in Pigs: Extensive Analysis of Copy Number Variation, Heterozygosity, Expression, and Breed Specificity

Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research

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