A new model defines the minimal set of polymorphism in HLA-DQ and -DR that determines susceptibility and resistance to autoimmune diabetes

Table 2 Clustering of HLA alleles in the space defined by the polar polymorphic residues in P9

β9	β37	β57	Alleles and association with type 1 diabetes
Polar	Polar	non-Asp	*DRB10405, DRB10409, DRB10801, DRB10901, DRB11303, DQB105,* *DQB10302, DQB10604*
Polar	Polar	Asp	*DRB10301, DRB10401, DRB10402*, DRB10403, *DRB10404*, DRB10406, *DRB10407, DRB10408, DQB10301, DQB10303, DQB10603, *DRB50200, DRB30202, DRB11301, DRB111, DRB110, DRB1*1402
Polar	Hydrophobic	non-Asp	DQB10201, DRB30101, DRB1*12
Polar	Hydrophobic	Asp	DRB11401, DRB111
Hydrophobic	Polar	non-Asp	none
Hydrophobic	Polar	Asp	DQB10601, DQB10602, DRB11501, DRB116, DRB1*0101
Hydrophobic	Hydrophobic	non-Asp	DRB1*07
Hydrophobic	Hydrophobic	Asp	none

HLA alleles are placed in the table based on whether the markers β9 and β37 are polar or hydrophobic and whether or not they retain the strongly conserved aspartic acid at β57. Susceptible molecules are shown in bold, neutral in normal text, and those that confer protection are shown in italics. All HLA molecules susceptible to autoimmune diabetes possess polar residues at β9 and β37. The combination of β9 and β37 suffice to describe susceptibility to type 1 diabetes, active protection or resistance (neutral). Non-Asp β57 is a modifier. DRB1*0406 has the short Ser at β37. DRB1*0403 may be neutral or protective. DRB1*0101 also has Ser at β37 which is not effective in conferring dominant protection. This analysis does not find DQ2 (DQB1*0201) to be high risk and it is proposed to be non-disposing. Disease association is taken from the literature as in Table 1 [Table S1 (Additional file 2)].

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