THE HUMAN MAST-CELL RECEPTOR-BINDING SITE MAPS TO THE 3RD CONSTANT DOMAIN OF IMMUNOGLOBULIN-E

The characterization of the site on the IgE molecule which accommodates the high affinity receptor for IgE (Fc-epsilon-RI) should allow the design of IgE analogues which can be utilized to block allergic responses. Using chimeric human IgE molecules in which different constant region domains were exchanged with their murine homologues, we demonstrate here that the C-epsilon-3 in its native configuration is essential for the binding to the alpha-subunit of the human Fc-epsilon-RI. Deletion of the human C-epsilon-2 from such chimeric molecules did not impair their ability to interact with the Fc-epsilon-RI, indicating that C-epsilon-2 is not directly involved in the human Fc-epsilon-RI binding site and that C-epsilon-3 alone is necessary and sufficient to account for most of the human Fc-epsilon-RI-binding capacity.