Phage display of peptide/major histocompatibility complex

Abstract

To date, there is no direct way to determine the antigenic specificity of T-cells. While B-cell epitopes can be selected from phage-displayed libraries of peptides, the corresponding molecular tool for identifying T-cell epitopes does not yet exist. The natural ligands of the T-cell antigen-receptor (TCR) are essentially antigenic peptides (P) associated with the products of the major histocompatibility complex (MHC). Here, we report phages displaying P–MHC complexes. Single-chain P–MHC class I molecules, produced in E. coli periplasm, stimulate T-cells in a peptide-specific fashion. The same P–MHC, fused at the tip of filamentous phage, directed their binding to a recombinant TCR restricted to the displayed MHC haplotype (H-2K d). Importantly, the binding of P–K d-fd to a K d-restricted TCR, and also to K d-restricted T-cell hybridomas, was modulated by the displayed peptide. Therefore, we suggest phage display of P–MHC as a direct molecular tool for probing T-cell specificity, and for selecting TCR ligands from genetic libraries encoding randomized or natural peptides.