Combined effect of glutamine at position 70 of HLA-DRB1 and alanine at position 57 of HLA-DQB1 in type 1 diabetes: An epitope analysis

PloS One
Petroula GerasimouPaul A Costeas

Abstract

The contribution of specific HLA Class II alleles in type 1 diabetes is determined by polymorphic amino acid epitopes that direct antigen binding therefore, along with conventional allele frequency analysis, epitope analysis can provide important insights into disease susceptibility. We analyzed the highly heterogeneous Cypriot population for the HLA class II loci of T1DM patients and controls and we report for the first time their allele frequencies. Within our patient cohort we identified a subgroup that did not carry the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04:xx-DQA1*03:01-DQB1*03:02 risk haplotypes but a novel recombinant one, DRB1*04:XX-DQA1*03:01-DQB1*02:01 designated DR4-DQ2.3. Through epitope analysis we identified established susceptibility (DQB1 A57, DRB1 H13) and resistance (DQB1 D57) residues as well as other novel susceptibility residues DRB1 Q70, DQB1 L26 and resistance residues DRB1 D70, R70 and DQB1 Y47. Prevalence of susceptibility epitopes was higher in patients and was not exclusively a result of linkage disequilibrium. Residues DRB1 Q70, DQB1 L26 and A57 and a 10 amino acid epitope of DQA1 were the most significant in discriminating risk alleles. An extended haplotype containing these epitopes was carr...Continue Reading

References

Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·G T HornH A Erlich
Dec 1, 1995·Seminars in Immunology·P H SchaferT S Jardetzky
Jul 18, 2002·Human Immunology·Janelle A NobleHenry A Erlich
Sep 28, 2005·Diabetes·Patrick ConcannonUNKNOWN Type 1 Diabetes Genetics Consortium
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ruth A EttingerWilliam W Kwok
Aug 17, 2006·Diabetic Medicine : a Journal of the British Diabetic Association·UNKNOWN DIAMOND Project Group
Oct 24, 2007·Trends in Biochemical Sciences·Lu Deng, Roy A Mariuzza
Nov 16, 2007·Nature·Sergey NejentsevUNKNOWN Wellcome Trust Case Control Consortium
Nov 27, 2007·Pediatric Diabetes·M P BahílloUNKNOWN Castilla-León Childhood Type 1 Diabetes Epidemiology Study Group
Jan 30, 2009·Diabetes, Obesity & Metabolism·J M M HowsonUNKNOWN Type 1 Diabetes Genetics Consortium
May 12, 2009·Nature Genetics·Jeffrey C BarrettUNKNOWN Type 1 Diabetes Genetics Consortium
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Brian D StadinskiJohn W Kappler
Aug 28, 2010·Diabetes·Janelle A NobleUNKNOWN Type 1 Diabetes Genetics Consortium
Sep 14, 2011·Current Diabetes Reports·Janelle A Noble, Ana M Valdes
Mar 1, 2012·The Journal of Biological Chemistry·Stig TollefsenChu-Young Kim
Mar 28, 2012·Hormones : International Journal of Endocrinology and Metabolism·Nicos SkordisVassos Neocleous
Dec 21, 2013·Diabetes·Christina L RoarkBrian M Freed
Oct 2, 2015·Human Immunology·Nezih CerebSoo Young Yang
Apr 16, 2016·International Journal of Immunogenetics·P GerasimouP Costeas

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
dissection

Software Mentioned

HistoGenetics
SKDM HLA Tool beta
SKDM HLA Tool

Related Concepts

Related Feeds

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.