Recombinant antibodies with T-cell receptor-like specificity: novel tools to study MHC class I presentation

Abstract

MHC class I molecules play a central role in the immune response against a variety of cells that have undergone malignant transformation by shaping the T cell repertoire and by presenting peptide antigens from endogeneous antigens to CD8+ cytotoxic T cells. Because of their unique specificity such MHC-peptide complexes are a desirable target for novel approaches in immunotherapy. Targeted delivery of toxins or other cytotoxic drugs to cells which express specific MHC-peptide complexes that are involved in the immune response against cancer or viral infections would allow for a specific immunotherapeutic treatment of these diseases. We have recently demonstrated that antibodies with the antigen-specific, MHC restricted specificity of T cells can be generated by taking advantage of the selection power of phage display technology. In addition to their tumor targeting capabilities antibodies that mimic the fine specificity of T cell receptors can serve as valuable research reagents that enable to study human class I peptide-MHC ligand-presentation as well as TCR-peptide-MHC interactions. T-cell receptor-like antibody molecules may prove to be useful tools for studying MHC class I antigen presentation in health and disease as well as for therapeutic purposes in cancer, infectious diseases, and autoimmune disorders.