page_title: HLA-DQ2
section_title: In celiac disease
hierarchical_section_title: HLA-DQ2 / In celiac disease
caption_attribution_description: English: Illustration of a2-gliadin showing the DQ2.5 restricted T-cell epitopes.
context_page_description: HLA-DQ2 is a serotype group within HLA-DQ serotyping system. The serotype is determined by the antibody recognition of β² subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.
  DQ2 is most common in Western Europe, North Africa and East Africa. Highest frequencies are observed in parts of Spain and Ireland; this distribution correlates with the frequency of two of the most prevalent autoimmune diseases. There is also an increase in DQB1*0201 in Central Asia, peaking in Kazakhstan and declining slowly west to east into China and finally Southeast Asia. DQA1*0501: DQB1*0201. DQ2.5 is one of the most predisposing factors for autoimmune disease.
  DQ2.5 is encoded, often, by a haplotype associated with a large number of diseases.
context_section_description: DQ2 represents the second highest risk factor for coeliac disease, the highest risk is a close family member with disease. Due to its link to coeliac disease, DQ2 has the highest association of any HLA serotype with autoimmune disease, close to 95% of all coeliacs have DQ2, of that 30% have 2 copies of DQ2. Of the DQ2 homozygotes who eat wheat, lifelong risk is between 20 and 40% for coeliac disease.
  
  The relationship of DQ2 and coeliac disease, however, is complex because there are multiple DQ2 isoforms. The DQ  α⁵β² (DQ2.5) isoform is strongly associated with CD. This isoform is partially encoded by the DQB1*02 genes in HLA-DQ2 positive individuals.  DQB1*0201 is genetically linked to DQA1*0501 forming the DQ2.5 haplotype that encodes both α⁵ and β² subunits. The DQ2.5 haplotype confers the single highest genetic risk for disease, however comparable risk can also come from very similar alleles on different haplotypes.
  The immunodominant site for DQ2.5 is on α2-gliadin. The site is a protease resistant 33mer that has 6 overlapping DQ2.5 restricted epitopes. This creates very strong binding of T-cells for DQ2.5-33mer complexes. DQ2.5 binds gliadin, but the binding is sensitive to deamidation caused by tissue transglutaminase. In almost all case the highest affinity sites of gluten are derived by deamidation. The HLA DQB1*0202 and its linked DQA1* alleles (the DQ2.2 haplotype) do not produce the α⁵ subunit. While the DQ2.2 heterodimer cannot effectively present α-2 gliadin, it can present other gliadins. In at least 1% of coeliacs DQ2.2 confers adaptive immunity to gliadin permitting coeliac disease.
caption: Illustration of deamidated alpha-2 gliadin's 33mer showing the overlapping of three varieties of T-cell epitope.
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