EPITOPE-MEDIATED ANTIGEN PREDICTION

摘要

There are many clinical instances in which, during the course of a disease, a patient may produce an antibody directed to unknown protein target(s). The targeted antigen(s) may be autoantigens (e.g., autoimmune diseases), microbial antigens (e.g., infectious diseases), allergens or, as in the case of B lymphoproliferative disorders and monoclonal gammopathies, antigens of unknown identity. When the antigen source is known or suspected, it may be feasible to construct a cDNA expression library and identify it. However, with no clues as to the antigen's origin, expression screening is impossible. We describe a new search strategy to overcome this limitation. We term the approach Epitope-Mediated Antigen Prediction (E-MAP). The technology enables one to link antibodies of unknown specificity to their cognate/target antigens in the protein database without requiring prior knowledge of their cellular source. We also describe a clinical application of the E-MAP technology to the study of multiple myeloma. In this study, we identified the protein target of paraproteins from a number of patients with multiple myeloma. These methods will be useful in biomarker discovery, clinical diagnostics, and therapeutic drug lead identification.