The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or
disease state, wherein the peptides are displayed in the context of
HLA molecules. These antibodies will mimic the specificity of a
T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-
cell receptor mimic of the present invention includes identifying
a peptide of interest, wherein the
peptide of interest is capable of being presented by an MHC molecule. Then, an
immunogen comprising at least one
peptide / MHC complex is formed, wherein the
peptide of the peptide / MHC complex is the peptide of interest. An effective amount of the
immunogen is then administered to a host for eliciting an immune response, and serum collected from the host is assayed to determine if desired antibodies that recognize a three-dimensional presentation of the peptide in the binding groove of the MHC molecule are being produced. The desired antibodies can differentiate the peptide / MHC complex from the MHC molecule alone, the peptide alone, and a complex of MHC and irrelevant peptide. Finally, the desired antibodies are isolated.