HLA class II polymorphism contributes to specify desmoglein derived peptides in pemphigus vulgaris and pemphigus foliaceus

Susceptibility to Pemphigus, an autoimmune disease of the skin, has been pr eviously linked to DRB1*0402, 1401/04 and DQB1*0503 in pemphigus vulgaris ( PV), to DRB1*0102, 0404, 1402/06 in endemic pemphigus foliaceus in Brazil a nd to DRB1*04 in Italian patients suffering from pemphigus foliaceus (PF). The disease is caused by autoantibodies against desmoglein (Dsg1 in PF, Dsg 3 in PV). Molecular typing of 57 French patients suffering from PV (37) and from PF ( 20) confirmed previous results concerning PV and showed that DRB1*0102 and 0404 are susceptible molecules to PF in France. We have analysed the characteristics of the 'pockets' of the susceptibility -associated molecules to PV and PF and we showed that (i) in PV, two kinds of Dsg3 derived peptides may be presented by HLA-DR according to HLA polymo rphism (DRB1*0402 or DRB1*14/0406), (ii) the same Dsg1 peptides may be pres ented by DRB1*0102, DQB1*0404 or DRB1*14 in PF, (iii) the DRB1*14/0406 PV-r elated molecules may be able to present Dsg1 and Dsg3 peptides thereby prov iding an explanation for the cases of PV with combined responses to Dsg1 an d to Dsg3 which are typified by a muco-cutaneous clinical phenotype. (C) 20 00 Academic Press.