High‐resolution HLA‐DQB1 typing using the polymerase chain reaction and sequence‐specific primers

Mullighan, Charles G.; Bunce, Michael; Ki, Welsh

doi:10.1111/j.1399-0039.1997.tb02936.x

Cited by 17 publications

(11 citation statements)

References 24 publications

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“…HLA DQB and HLA DQA genotyping (Bunce et al, 1995;Mullighan et al, 1997;Olerup et al, 1993) of 91 subjects in Oxford and 204 celiac disease subjects in Melbourne identified 12 (five in Oxford and seven in Melbourne) that possessed HLA DQ8 (HLA DQA1*03 and HLA DQB1*0302) but not genes encoding HLA DQ2 (either HLA DQA1*05 or HLA DQB1*02), among whom five underwent the gluten challenge. Blood from two further celiac subjects who possessed both HLA DQ2 and DQ8 but did not undergo the gluten challenge was used to clone T cells.…”

Section: Subjects and Antigen Challengementioning

confidence: 99%

A Structural and Immunological Basis for the Role of Human Leukocyte Antigen DQ8 in Celiac Disease

et al. 2007

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The risk of celiac disease is strongly associated with human leukocyte antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the pathogenesis of HLA-DQ2-mediated celiac disease is established, the underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac pathology were indeed HLA DQ8 restricted and that multiple, mostly deamidated peptides derived from protease-sensitive sites of gliadin were recognized. This pattern of reactivity contrasted with the more absolute deamidation dependence and relative protease resistance of the dominant gliadin peptide in DQ2-mediated disease. We provided a structural basis for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The data established that the molecular mechanisms underlying HLA-DQ8-mediated celiac disease differed markedly from the HLA-DQ2-mediated form of the disease. Accordingly, nondietary therapeutic interventions in celiac disease might need to be tailored to the genotype of the individual.

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Section: Subjects and Antigen Challengementioning

confidence: 99%

A Structural and Immunological Basis for the Role of Human Leukocyte Antigen DQ8 in Celiac Disease

et al. 2007

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“…HLA-DQA and HLA-DQB genotypes were determined using peripheral blood DNA and polymerase chain reaction with sequence specific primer mixes. [24][25][26] HLA-DQ genotype data for subjects is shown in table 2.…”

Section: Subjects and Antigen Challengementioning

confidence: 99%

T cells in peripheral blood after gluten challenge in coeliac disease

Anderson

Heel²,

Tye–Din³

et al. 2005

Gut

121

128

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Background: Current understanding of T cell epitopes in coeliac disease (CD) largely derives from intestinal T cell clones in vitro. T cell clones allow identification of gluten peptides that stimulate T cells but do not quantify their contribution to the overall gluten specific T cell response in individuals with CD when exposed to gluten in vivo. Aims: To determine the contribution of a putative dominant T cell epitope to the overall gliadin T cell response in HLA-DQ2 CD in vivo. Patients: HLA-DQ2+ individuals with CD and healthy controls. Methods: Subjects consumed 20 g of gluten daily for three days. Interferon c (IFN-c) ELISPOT was performed using peripheral blood mononuclear cells (PBMC) to enumerate and characterise peptide and gliadin specific T cells before and after gluten challenge. Results: In 50/59 CD subjects, irrespective of homo-or heterozygosity for HLA-DQ2, IFN-c ELISPOT responses for an optimal concentration of A-gliadin 57-73 Q-E65 were between 10 and 1500 per million PBMC, equivalent to a median 51% of the response for a ''near optimal'' concentration of deamidated gliadin. Whole deamidated gliadin and gliadin epitope specific T cells induced in peripheral blood expressed an intestinal homing integrin (a4b7) and were HLA-DQ2 restricted. Peripheral blood T cells specific for A-gliadin 57-73 Q-E65 are rare in untreated CD but can be predictably induced two weeks after gluten exclusion. Conclusion: In vivo gluten challenge is a simple safe method that allows relevant T cells to be analysed and quantified in peripheral blood by ELISPOT, and should permit comprehensive high throughput mapping of gluten T cell epitopes in large numbers of individuals with CD.

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“…After the repetition, it was concluded that the primers described by Olerup et al and Mullighan et al 15,16 can be moderately/highly discriminatory in other populations, but have failed to discriminate the alleles at the Ã 06 locus in our series of Brazilian pregnant women belonging to a population with a high degree of racial miscegenation. Therefore, as the problem took place in both studied groups (with and without toxoplasmosis), we analyzed the DQB1 alleles results at the Ã 06 locus as a whole (locus DQB1 Ã 06), and no statistical difference was found between the two groups.…”

Section: Discussionmentioning

confidence: 99%

HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis

et al. 2016

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Host and parasite genotypes are among the factors associated with congenital toxoplasmosis pathogenesis. As HLA class II molecules play a key role in the immune system regulation, the aim of this study was to investigate whether HLA-DQA1/B1 alleles are associated with susceptibility or protection to congenital toxoplasmosis. One hundred and twenty-two fetuses with and 103 without toxoplasmosis were studied. The two study groups were comparable according to a number of socio-demographic and genetic variables. HLA alleles were typed by PCR-SSP. In the HLA-DQA1 region, the allele frequencies showed that Ã 01:03 and Ã 03:02 alleles could confer susceptibility (ORD 3.06, p D 0.0002 and ORD 9.60, pD 0.0001, respectively) as they were more frequent among infected fetuses. Regarding the HLA-DQB1 region, the Ã 05:04 allele could confer susceptibility (OR D 6.95, p < 0.0001). Of the 122 infected fetuses, 10 presented susceptibility haplotypes contrasting with only one in the non-infected group. This difference was not statistically significant after correction for multiple comparison (OR D 9.37, pD0.011). In the casuistic, there were two severely damaged fetuses with high parasite loads determined in amniotic fluid samples and HLA-DQA1 susceptibility alleles. In the present study, a discriminatory potential of HLA-DQA1/B1 alleles to identify susceptibility to congenital toxoplasmosis and the most severe cases has been shown.

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High‐resolution HLA‐DQB1 typing using the polymerase chain reaction and sequence‐specific primers

Cited by 17 publications

References 24 publications

A Structural and Immunological Basis for the Role of Human Leukocyte Antigen DQ8 in Celiac Disease

A Structural and Immunological Basis for the Role of Human Leukocyte Antigen DQ8 in Celiac Disease

T cells in peripheral blood after gluten challenge in coeliac disease

HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis

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