Polymorphism of sheep MHC Class IIb gene TAPASIN

Subramaniam, N. Siva; Morgan, Eleanor; Lee, C.; Wetherall, J. D.; Groth, David

doi:10.1016/j.vetimm.2010.04.018

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Thus, not only can polymorphisms at these residues impact their interaction with tapasin, but the specific residues that are most significant in our study have been previously identified by biochemical experiments. Overall, tapasin is thought to be under purifying selection, being well conserved across species with 84% amino acid identity between human and sheep . This implies that there is selection pressure to maintain the sequence of tapasin and the coding SNP is likely to be the most relevant due to its potential for functional interaction with HLA or ERp57.…”

Section: Discussionmentioning

confidence: 99%

“…Overall, tapasin is thought to be under purifying selection, being well conserved across species with 84% amino acid identity between human and sheep. 40 This implies that there is selection pressure to maintain the sequence of tapasin and the coding SNP is likely to be the most relevant due to its potential for functional interaction with HLA or ERp57. Tapasin is thus likely to be important in generating optimal HLA class I peptide repertoires in the antiviral immune response.…”

Section: Discussionmentioning

confidence: 99%

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Synergism of Tapasin And Human Leukocyte Antigens in Resolving Hepatitis C Virus Infection

et al. 2013

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CD8+ T cell responses to hepatitis C virus (HCV) are important in generating a successful immune response and spontaneously clearing infection. HLA class I presents viral peptides to CD8+ T cells to permit detection of infected cells, and tapasin is an important component of the peptide loading complex for HLA class I. We sought to determine if tapasin polymorphisms affected the outcome of HCV infection. Patients with resolved or chronic HCV infection were genotyped for the known C/G coding polymorphism in exon 4 of the tapasin gene. In a European, but not a US, Caucasian population, the tapasin G allele was significantly associated with outcome of HCV infection, being found in 82.5% of resolvers versus 71.3% of persistently infected individuals (p=0.02, OR=1.90 95% CI=1.11–3.23). This was more marked at the HLA-B locus at which heterozygosity of both tapasin and HLA-B was protective (p<0.03). Individuals with an HLA-B allele with an aspartate at residue 114 and the tapasin G allele were more likely to spontaneously resolve HCV infection (p<0.00003, OR=3.2 95%CI=1.6–6.6). Additionally individuals with chronic HCV and the combination of an HLA-B allele with an aspartate at residue 114 and the tapasin G allele also had stronger CD8+ T cell responses (p=0.02, OR=2.58, 95% CI-1.05–6.5). Conclusion Tapasin alleles contribute to the outcome of HCV infection by synergising with polymorphisms at HLA-B in a population specific manner. This polymorphism may be relevant for peptide vaccination strategies against HCV infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Synergism of Tapasin And Human Leukocyte Antigens in Resolving Hepatitis C Virus Infection

et al. 2013

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“…Albers et al (1987) postulated that one ram 'the Golden Ram' carried a major single resistance gene having a function to decrease FEC by an amount equivalent to two standard deviations. The relationship between genes of the ovine major histocompatibility complex and resistance to H. contortus remained under study, and it has been shown that this is the densest region in the genome that is having significant links with disease (Siva Subramaniam et al 2010). The interferon gamma (IFN-γ) gene has received much attention because of its proposed association with nematode resistance.…”

Section: Resistant Genesmentioning

confidence: 99%

Small ruminant resistance against gastrointestinal nematodes: a case of Haemonchus contortus

et al. 2011

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Gastrointestinal nematode (GIN) infections are a common constraint to small ruminant industry throughout the world, and among those, haemonchosis has its own significance. Control of GIN primarily relies on the use of anthelmintics, but this approach has become less reliable due to the development of resistance in GINs against commonly used anthelmintics and an increased consumer demand for environmentally friendly animal products. These issues have stimulated investigations to find alternative sustainable control strategies, which are less reliant on anthelmintic input. One of such strategies is breeding of small ruminants for their resistance to the GINs. The susceptibility and resistance of animals to GIN infections varies within and between breeds. Various parasitological, biochemical and immunological parameters are employed to evaluate natural resistance status of animals both in natural pasture and artificial infections. The immune mechanisms responsible for resistance are not completely understood, but it has a significant effect in inherited resistance. Relatively resistant or tolerant animals show better local and generalised immune response as compared to susceptible. Immune response against GINs is influenced by many physiological factors. Determination of specific genes linked with host resistance will provide a valuable approach to find out the molecular mechanism of host resistance to GINs. Resistance has been reported to reduce pasture contamination, which in turn reduces re-infection and thus the requirement of the frequent anthelmintic treatments. The efficiency of control can be increased through objective and accurate identification of genetically tolerant individuals by natural and artificial infections with GINs. Complete resistance is the ultimate solution, but this has generally been ignored as a commercial reality. This paper reviews the published reports on natural resistance in small ruminants and discusses the prospects of developing small ruminants, which could be resistant to GINs.

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Characterization of the sheep Complement Factor B gene (CFB)

Qin

Munyard

Lee

et al. 2011

Veterinary Immunology and Immunopathology

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The Complement Factor B gene (CFB) of the alternative complement pathway has been identified in the sheep Major Histocompatibility Complex (MHC) and its genomic sequence determined. CFB is located approximately 600 bp upstream of the complement C2 gene, contains 18 exons, and manifests the domain signature characteristic of CFB protein. Thirteen single nucleotide polymorphisms were identified in merino sheep and interbreed variation was identified by comparison with International Sheep Genomics Consortium data. Two predicted non synonymous substitutions were observed and in-silico analysis indicates that these are likely to have a destabilizing effect on the protein structure. Sheep and cattle CFB were compared and shown to contain a common nine nucleotide deletion in exon 18 relative to human CFB. Predicted CFB amino acid sequences for these two species contain 761 aa relative to 764 aa in the human orthologue. Sequencing of the cosmid and BAC clones used in this study permitted the relative positions of three adjacent loci to be determined and showed that the previously described microsatellite locus (BfMs) is located within SKIV2L.

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Polymorphism of sheep MHC Class IIb gene TAPASIN

Cited by 4 publications

References 26 publications

Synergism of Tapasin And Human Leukocyte Antigens in Resolving Hepatitis C Virus Infection

Synergism of Tapasin And Human Leukocyte Antigens in Resolving Hepatitis C Virus Infection

Small ruminant resistance against gastrointestinal nematodes: a case of Haemonchus contortus

Characterization of the sheep Complement Factor B gene (CFB)

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