Allergenicity of proteins is a subtle property encoded in their structures. In the host antigen-presenting cells, the allergens are processed as antigens by the means of human leukocyte antigens (HLA) class II proteins. HLA class II proteins are involved in both antigen recognition by T cells and in B cells activation.

HLA proteins are extremely polymorphic and polygenic. HLAs class II contain three loci: DR, DQ and DP, which contribute to a different extend for the immune response. Although the structure of the HLA proteins allows binding of peptides with different length, the binding core of the peptide is only 9 amino acid long.

Cross-reactivity measures the extent to which different antigens appear similar to the immune system. Although in allergy cross-reactivity is usually concerned as phenomenon of an IgE antibody recognizing, binding, and inducing an immune response to similar allergenic molecules from different species, there are evidences for a strong connection between immune system reaction to allergens and T cell epitope recognition

AllerScreener is a tool for allergenicity and cross-reactivity prediction based on the abilities of allergenic proteins to generate binders to HLA class II proteins. The generated peptides are compared to HLA binders originating from known allergens. The server returns a list of common binders, origin proteins and species. Different species generate common HLA binders and this determines their cross-reactivity.