%0 Journal Article
%T Modeling the bound conformation of Pemphigus Vulgaris-associated peptides to MHC Class II DR and DQ Alleles
%A Tong Joo
%A Bramson Jeff
%A Kanduc Darja
%A Chow Selwyn
%J Immunome Research
%D 2006
%I 
%R 10.1186/1745-7580-2-1
%X Background Pemphigus vulgaris (PV) is a severe autoimmune blistering disorder characterized by the presence of pathogenic autoantibodies directed against desmoglein-3 (Dsg3), involving specific DR4 and DR6 alleles in Caucasians and DQ5 allele in Asians. The development of sequence-based predictive algorithms to identify potential Dsg3 epitopes has encountered limited success due to the paucity of PV-associated allele-specific peptides as training data. Results In this work we constructed atomic models of ten PV associated, non-associated and protective alleles. Nine previously identified stimulatory Dsg3 peptides, Dsg3 96每112, Dsg3 191每205, Dsg3 206每220, Dsg3 252每266, Dsg3 342每356, Dsg3 380每394, Dsg3 763每777, Dsg3 810每824 and Dsg3 963每977, were docked into the binding groove of each model to analyze the structural aspects of allele-specific binding. Conclusion Our docking simulations are entirely consistent with functional data obtained from in vitro competitive binding assays and T cell proliferation studies in DR4 and DR6 PV patients. Our findings ascertain that DRB1*0402 plays a crucial role in the selection of specific self-peptides in DR4 PV. DRB1*0402 and DQB1*0503 do not necessarily share the same core residues, indicating that both alleles may have different binding specificities. In addition, our results lend credence to the hypothesis that the alleles DQB1*0201 and *0202 play a protective role by binding Dsg3 peptides with greater affinity than the susceptible alleles, allowing for efficient deletion of autoreactive T cells.
%U http://www.immunome-research.com/content/2/1/1