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- Title
Mimotopes for Alloreactive and Conventional T Cells in a Peptide–MHC Display Library.
- Authors
Crawford, Frances; Huseby, Eric; White, Janice; Marrack, Philippa; Kappler, John W
- Abstract
The use of peptide libraries for the identification and characterization of T cell antigen peptide epitopes and mimotopes has been hampered by the need to form complexes between the peptides and an appropriate MHC molecule in order to construct a complete T cell ligand. We have developed a baculovirus-based peptide library method in which the sequence encoding the peptide is embedded within the genes for the MHC molecule in the viral DNA, such that insect cells infected with virus encoding a library of different peptides each displays a unique peptide–MHC complex on its surface. We have fished in such a library with two different fluorescent soluble T cell receptors (TCRs), one highly peptide specific and the other broadly allo-MHC specific and hypothesized to be much less focused on the peptide portion of the ligand. A single peptide sequence was selected by the former αβTCR that, not unexpectedly, was highly related to the immunizing peptide. As hypothesized, the other αβTCR selected a large family of peptides, related only by a similarity to the immunizing peptide at the p5 position. These findings have implications for the relative importance of peptide and MHC in TCR ligand recognition. This display method has broad applications in T cell epitope identification and manipulation and should be useful in general in studying interactions between complex proteins. A baculovirus expression library -- encoding peptides in the context of MHC molecules -- has been developed to identify and characterize unique peptide-MHC complexes that bind specific T cell receptors.
- Subjects
T cell receptors; T cells; PEPTIDES; AMINO acid sequence; IMMUNE response; VIRAL DNA
- Publication
PLoS Biology, 2004, Vol 2, Issue 4, p1
- ISSN
1544-9173
- Publication type
Article
- DOI
10.1371/journal.pbio.0020090