Laboratory of Biochemistry
Te Piao King
Many proteins in our environment, from diverse sources such as foods, insects or pollens, can cause IgE-mediated allergy in susceptible people. Some of these proteins are highly potent allergens even in minute amounts. The immunogenicity of a protein is controlled partly by the genetic makeup of the host, and may also be partly controlled by the chemical nature of the proteins, which determines their processing by antigen-presenting cells and the accessibility of their T and B cell epitopes. Together these factors can influence the magnitude and the isotype distribution of antibody responses in the immunized host. Our general objectives are to learn which immunochemical properties of a protein, if any, are important for its immunogenicity as an allergen and how we might be able to use such properties for the treatment of allergic diseases.
Our findings suggest that the strong immunogenicity of allergens may be related in part to their having cross-reacting T and B cell epitopes with other proteins in our environment. Thus susceptible persons may be primed for immune responses to particular allergens because of their prior exposure to other cross-reacting proteins. This hypothesis is based on the following observations. In recent years the primary structures and the biologic functions of a number of allergens from pollens, mites and other sources have been established. And we have cloned and sequenced the three major allergens of hornet venom. One has phospholipase A1 activity, another has hyaluronidase activity and the third designated as antigen 5 is of unknown biologic function. The only noticeable common feature of these allergens from various sources is their sequence similarity with other proteins in our environment. For example, hornet antigen 5 and hyaluronidase both have sequence similarity with mammalian testis proteins, and hornet phospholipase has similarity with mammalian lipases. Hornet antigen 5 also has similarity with a class of plant pathogenesis-related proteins. Antigenic cross reactivity of hornet and mammalian proteins was detected in mice. Studies are being made to determine their cross reacting T and B cell epitopes.
Another focus of our research has been the bee venom allergen melittin. This 26-residue peptide, the smallest allergen known, induces IgE and IgG responses in allergic patients and in selected strains of mice. The small size of melittin makes it a useful model to study how changes in the structure of an immunogen can alter its presentation to immunocytes which in turn can lead to modulation of T and B cell responses. In the murine system the major T and B cell epitopes of melittin are located in the regions of residue 11-19 and 20-26 respectively. Studies with truncated or transposed analogs show that the immunogenicity of melittin for antibody response depends on the membrane binding activity of the NH2-terminal portion of melittin followed with oligomer formation in the lipid bilayer. Truncated melittin analogs containing its T cell epitope induced suppression of T and B cell responses when mice were pretreated with the analogs prior to their immunization with melittin.