While suppression of Ii gene expression can force cells to process antigens for class II presentation, the use of Ii-Key hybrids entirely bypasses the need for antigen processing. Antigen Express scientists discovered that a portion of the Ii protein interacts with an allosteric site on MHC class II molecules. The interaction of this portion of the molecule, termed Ii-Key, with the allosteric site loosens the hold of the antigenic binding trough on any resident epitope. Antigen Express scientists have shown that hybrid peptides containing the Ii-Key ligand linked to an antigenic epitope also bind to MHC Class II molecules and discharge resident antigens from the antigen binding groove, as illustrated in Figure 2. When the Ii-Key end of the hybrid binds to the MHC Class II molecule, it constrains the antigenic end to a region close to the MHC Class II antigen binding groove. This anchoring compensates for the reduced binding affinity of the groove, so the hybrid antigen can occupy it and be presented to T helper cells. By these means, Ii-Key hybrids bypass all requirements for antigen processing and directly 'hijack' MHC class II molecules already on the surface of cells to present whatever epitope is present in the hybrid.

Ii-Key hybrid peptides are being used to selectively activate two different classes of T helper cell responses (Th1 responses, which increase the intensity and duration of the immune response, or Th2 responses, which induce immunotolerance) depending on how the peptides are administered. The use of Ii-Key hybrid peptides to induce primarily Th1 responses overcomes a critical limitation of peptide vaccines; i.e., their general lack of ability to elicit T helper cell responses that are required for a robust and long lived response. There are active programs at Antigen Express targeting both cancer and infectious diseases using hybrids to stimulate the Th1 response. Similarly, programs have been initiated to use Ii-Key hybrid peptides administered to selectively activate Th2 responses and thereby induce tolerance to antigens involved in harmful immune reactions, e.g. autoimmunity, allergy, and transplant rejection.

» return to top