As a danger signal �C a type of stimulus which is thought to play an important role in the regulation of immune responses. Airborne allergens bearing nitro-tyrosine mimic nitrated foreign proteins present in inflamed tissue, which may explain our findings that nitration of allergens intensifies the presentation of allergen derived HLA-DR associated peptides. Previous studies have shown increased immunogenicity of Bet v 1 nitro compared to Bet v 1: Sera from patients with birch pollen allergy contain higher titers for IgE against Bet v 1 nitro compared to Bet v1; the reactivity against Bet v 1 nitro cannot be fully removed by absorption with normal Bet v 1, indicating a specific recognition of the nitrated allergen. The same study showed that nitrated Bet v 1 and nitrated Ovalbumin were more potent allergens compared to their unmodified forms when tested in mouse models. Regarding the issue of HLA haplotypes and the predisposition to allergies published studies show diverging results. Several studies have shown associations between IgE reactivity and the presence of distinct Acipimox HLA-DRB1 alleles; most notably in patients allergic to ragweed Amb a 5, Alternaria Alt a 1, Parietaria Par o 1, birch Bet v 1, cat Fel d 1, as well as cockroach and house dust mite allergens. In these cases HLADRB1 haplotypes could favor susceptibility to allergy. However, Jahn-Schmid et al. have recently shown that the dominant T cell epitopes of the major ragweed allergen Amb a 1 were presented by different HLA- DR, DP and DQ molecules. These findings suggest that, alternatively, a broad HLA class II restriction profile might contribute to the high allergenic properties of Amb a 1. Several questions remain to be addressed, e.g. if and/or how nitrated proteins may interfere with uptake and/or processing pathways of DCs or if potential alternative uptake mechanisms for nitro-proteins e.g. via specialized receptors expressed on DCs might exist. Furthermore, the questions whether chemical nitration of the protein compared to nitration by NO2 and ozone in polluted air have different characteristics and whether they contribute to nitration to a similar extent could not be investigated in the scope of the present study. Environmental pollutants might nitrate tyrosine residues less eagerly and more selectively than the chemical agent used here. These aspects will have to be addressed in follow-up investigations. In summary, our data show that nitration has an enhancing effect on processing and presentation of Bet v 1 derived HLA-DR associated peptides, by enhancing both the quality and the quantity of the Bet v 1 specific Terbuthylazine peptide repertoire.