Fig 7.

Model for immunogenicity/allergenicity of an allergen depending on differential fold stability at different endosomal pH. During antigen uptake and processing, allergens face a broad range of different pH values, ranging from approximately 7.4 in the extracellular matrix to approximately 4.0 in the terminal lysosome. Proteins with low fold stability in the early endosome are proteolytically processed prematurely, resulting in poor antigen presentation because of low abundance of MHC class II in this compartment (“blue” protein). Proteins with high fold stability at low pH (“black” protein) remain structurally intact until they reach the terminal lysosome, where again MHC class II levels are low and antigen presentation is inefficient. Only proteins that survive the early endosome but are efficiently processed at a more acidic pH can accumulate in the late endosome, where they are finally degraded and loaded on highly abundant MHC II molecules (“red” protein).