Link to Pubmed [PMID] – 14768065
Eur. J. Immunol. 2004 Feb;34(2):598-607
Characterizing peptide epitopes targeted by major histocompatibility complex (MHC)-restricted T cells of unknown specificity would have broad implications. In this article we introduce and validate an original phage-displayed library of noncovalent complexes of peptide and MHC (P/MHC). We show that soluble MHC molecules associate with peptides presented by a phage, thereby resulting in the formation of multivalent P/MHC phages. Complex formation is stabilized by the interaction of the soluble partner (MHC) with two components, peptide and beta2-microglobulin, both of which are covalently linked to the phage. As proof of concept, we have used this strategy to express peptide libraries in the context of H-2K(b). Using monoclonal antibody 25D (specific for ovalbumin/H-2K(b)) as a template to screen the library, we were able to select a variant epitope functionally and structurally related to the wild-type peptide. Interaction studies between monoclonal antibody 25D and cells suggest that the variant peptide has been selected on the basis of a decreased dissociation rate between the peptide/H-2K(b) complex and its ligand. A weak agonist of the N15 TCR (vesicular stomatitis virus/H-2K(b)-specific) was also isolated from another P/MHC library. This strategy opens up new perspectives for antigen discovery and the manipulation of T cell responses.