| 摘要 |
The present invention relates to a methodology of producing antibodies th at recognize peptides associated with a tumorigenic or disease state, wherei n the peptides are displayed in the context of HLA molecules. These antibodi es will mimic the specificity of a T cell receptor (TCR) but will have highe r binding affinity such that the molecules may be used as therapeutic, diagn ostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherei n 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, wh erein 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 eliciti ng an immune response, and serum collected from the host is assayed to deter mine if desired antibodies that recognize a three-dimensional presentation o f the peptide in the binding groove of the MHC molecule are being produced. The desired antibodies can differentiate the peptide/MHC complex from the MH C molecule alone, the peptide alone, and a complex of MHC and irrelevant pep tide. Finally, the desired antibodies are isolated.
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