Recombinant antibodies with MHC-restricted, peptide-specific, T-cell receptor-like specificity: new tools to study antigen presentation and TCR-peptide-MHC interactions.

摘要: The advent in recent years of the application tetrameric arrays class I peptide-MHC complexes now enables us to detect and study rare populations antigen-specific CD8+ T cells. However, available methods cannot visualize or determine number distribution these TCR ligands on individual cells antigen-presenting (APCs) tissues. Here we describe a new approach that human ligand-presentation as well TCR-peptide-MHC interactions. Such studies are facilitated by applying novel tools form peptide-specific, HLA-A2-restricted recombinant antibodies directed toward large variety tumor-associated viral T-cell epitope peptides. Using antibody phage display library, panel specific for particular complex peptide-dependent, MHC-restricted manner was isolated. These were used directly MHC-peptide tumor cells, virus-infected flow cytometry. They enabled direct quantitation situ detection surface APCs after naturally occurring active intracellular processing cognate antigen. will enable also development targeting molecules deliver drugs toxins Thus, demonstrate our ability transform unique fine specificity but low intrinsic affinity TCRs into high-affinity soluble endowed with TCR-like epitopes. may prove be crucial useful studying MHC antigen presentation health disease therapeutic purposes cancer, infectious diseases autoimmune disorders.