Why are some proteins allergens?

The ability of certain proteins to induce an allergic response in susceptib le individuals is well established. Symptoms can range from mild erythema o r rhinitis, to acute, and possibly fatal, anaphylactic shock. Because such allergic responses require complex interactions between the protein and the immune system, they are notoriously difficult to predict. Nevertheless, it is clear that some proteins are intrinsically more allergenic than others. The challenge for toxicologists is to identify those characteristics that confer on proteins the potential to induce allergic sensitization and aller gic disease. Here, we first consider the potential contribution that indivi dual epitopes may make to the allergenicity of a protein. These are the min imal peptide units within proteins that can be recognized by the immune sys tem and are a fundamental requirement for all immune responses, including t hose resulting in allergic sensitization. It appears that allergens must ne cessarily contain B-cell epitopes to which immunoglobulin E (IgE) can bind, and T-cell epitopes capable of inducing a type 2 T-lymphocyte response. Ne vertheless, it appears doubtful that the presence of appropriate epitopes a lone is sufficient to endow a protein with allergenic potential. We therefo re consider also the contribution that other features and characteristics o f proteins may make to their overall allergenicity. In particular, we consi der the effects that resistance to proteolysis, post-translational glycosyl ation, and enzymatic activity may have. It appears that relative stability in simulated gastric fluid (SGF) sometimes correlates with allergenic activ ity. However, this is not universally true, and it is known that there are protein allergens, such as some of those associated with oral allergy syndr ome, that are unstable. Nevertheless, if stability in SGF is associated wit h the intrinsic allergenicity of many proteins irrespective of the route of exposure, then this may reflect some more fundamental property of proteins , and possibly their stability in other biologic matrices and/or to intrace llular proteases. Post-translational modification appears generally to enha nce allergenicity, perhaps by increasing uptake and detection of the protei n by the immune system. Some enzymatic activities also enhance allergenicit y through what appear to be several different mechanisms, including nonspec ific activation of cells participating in the immunologic response. Overall , it appears likely that many factors can contribute to the overall allerge nicity of any given protein. Some, such as the presence of epitopes with al lergenic potential, may be essential. Others, such as the glycosylation sta tus, resistance to proteolysis, and enzymatic activity, may play a subsidia ry but nevertheless critically important role. By better defining the limit s within which these factors operate, we can hope to gain a better understa nding of the fundamental origins of protein allergenicity, and therefore be in a position to identify and characterize the hazards and risks of allerg ic disease associated with novel proteins.