A PHAGE DISPLAY SYSTEM FOR DETECTION OF T-CELL RECEPTOR-ANTIGEN INTERACTIONS

The process of T cell recognition involves a complex set of interactio ns between the various components of the TCR/MHC/peptide trimolecular complex. We have developed a system for exploring the specific binding interactions contributed by the constituent subunits of TCR complexes for components of their ligands. We utilized an M13 phage display sys tem, designed for multivalent receptor display, to explore specific bi nding interactions between various TCR alpha chains and specific antig en in the absence of MHC. The multivalent TCR-phage display system was sensitive enough to reveal some TCR alpha chains capable of binding d irectly to antigen with the same fine specificity shown by the MHC-res tricted T cells from which the a chains were derived. Cross-specificit y analysis using two antigen-binding TCR alpha chains derived from T c ells with different polypeptide antigen specificities confirmed the fi delity of this binding. In mixtures of antigen-binding and non-binding TCR alpha-displaying phage, specific selection was achieved at a star ting frequency of 1/1000, suggesting that this system can be employed for selection and analysis of TCR-displaying phage libraries. While th e binding specificities exhibited by these TCRs are unusual, they prov ide a novel perspective from which to study the specific binding inter actions that constitute TCR antigen binding.