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. 2015 Jan 1;38(1):147–151. doi: 10.5665/sleep.4342

Figure 2.

Figure 2

(A) In celiac disease the majority of patients carry two predisposing alleles: DQA1*05 together with DQB1*02. The predisposing HLA genes do not have to be on the same chromosome but instead can also be on different chromosomes (trans). Heterodimerization of the alleles causes the risk alleles to form a HLA-heterodimer that can detect gluten-derived peptides, thus increasing the risk for celiac disease. (B,C) In narcolepsy, the allele competition model predicts decreasing DQ0602 availability in various genotype combinations. Similarly to celiac disease, the HLA-molecules can heterodimerize and affect the risk of narcolepsy. The DQ0602 homozygotes have the highest risk since they can present hypocretin autoantigen in all DQ0602 complexes. In contrast, those that carry one copy of DQ0602 and have DQA1*01 (not 01:02) at the other chromosome will be protected: DQA1*01 (not 01:02) can heterodimerize with DQB1*06:02 thus competing with DQA1*01:02 binding and reducing the amount of functional, hypocretin-presenting DQ0602. Carrying DQA1*01:02 at both chromosomes confers a modest increase in risk as DQB1*06:02 will be able to always bind with DQA1*01:02. DQB1*03:01 increases risk for narcolepsy which is not explained by the amount of available DQ0602. Data obtained from Tafti et al., 2014, and courtesy of the authors.