| Title |
Influence of HLA-DR and -DQ alleles on autoantibody recognition of distinct epitopes within the juxtamembrane domain of the IA-2 autoantigen in type 1 diabetes
|
|---|---|
| Published in |
Diabetologia, November 2015
|
| DOI | 10.1007/s00125-015-3803-5 |
| Pubmed ID | |
| Authors |
Carolyn C. Richardson, Kerry A. McLaughlin, Diana Morgan, Richard G. Feltbower, Michael R. Christie |
| Abstract |
Insulinoma-associated protein 2 (IA-2) is a major target of autoimmunity in type 1 diabetes. When first detected, IA-2-autoantibodies commonly bind epitopes in the juxtamembrane (JM) domain of IA-2 and antibody responses subsequently spread to the tyrosine phosphatase domain. Definition of structures of epitopes in the JM domain, and genetic requirements for autoimmunity to these epitopes, is important for our understanding of initiation and progression of autoimmunity. The aims of this study were to investigate the contribution of individual amino acids in the IA-2 JM domain to antibody binding to these epitopes and the role of HLA genotypes in determining epitope specificity. Regions of the JM domain recognised by autoantibodies were identified by peptide competition and inhibitory effects of alanine substitutions of residues within the JM region. Antibody binding was determined by radioligand binding assays using sera from patients genotyped for HLA-DRB1 and -DQB1 alleles. Patients were categorised into two distinct groups of JM antibody reactivity according to peptide inhibition. Inhibition by substitutions of individual amino acids within the JM domain differed between patients, indicating heterogeneity in epitope recognition. Cluster analysis defined six groups of residues having similar inhibitory effects on antibody binding, with three clusters showing differences in patients affected or unaffected by peptide. One cluster demonstrated significant differences in antibody binding between HLA-DRB1*04 and HLA-DRB1*07 patients and within DRB1*04 individuals; antibody recognition of a second cluster depended on expression of HLA-DQB1*0302. The results identify amino acids contributing to distinct epitopes on IA-2, with both HLA-DR and HLA-DQ alleles influencing epitope specificity. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 25% |
| Other | 2 | 13% |
| Student > Doctoral Student | 2 | 13% |
| Lecturer | 1 | 6% |
| Student > Bachelor | 1 | 6% |
| Other | 3 | 19% |
| Unknown | 3 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 25% |
| Biochemistry, Genetics and Molecular Biology | 3 | 19% |
| Psychology | 2 | 13% |
| Immunology and Microbiology | 1 | 6% |
| Agricultural and Biological Sciences | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 4 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 February 2016.
All research outputs
#14,828,686
of 22,833,393 outputs
Outputs from Diabetologia
#4,382
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#155,439
of 281,840 outputs
Outputs of similar age from Diabetologia
#52
of 69 outputs
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