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PMID: 15094798 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Mimotopes for alloreactive and conventional T cells in a peptide-MHC display library.

PLoS biology ·Vol. 2 ·No. 4 ·2004-04-00 ·Pages E90

Crawford F, Huseby E, White J, Marrack P, Kappler JW

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 alphabetaTCR that, not unexpectedly, was highly related to the immunizing peptide. As hypothesized, the other alphabetaTCR 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.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Monoclonal/chemistry B7-1 Antigen/chemistry Baculoviridae/metabolism Cell Line DNA, Viral/genetics Epitopes/chemistry Epitopes, T-Lymphocyte/chemistry Flow Cytometry Gene Library Histocompatibility Antigens Class I/chemistry Hybridomas/metabolism Insecta Intercellular Adhesion Molecule-1/metabolism Interleukin-2/metabolism Ligands Major Histocompatibility Complex Mice Mice, Inbred C57BL Molecular Sequence Data Oligonucleotides/chemistry Peptide Library Peptides/chemistry Receptors, Antigen, T-Cell/metabolism Sequence Analysis, DNA Sequence Homology, Amino Acid T-Lymphocytes/immunology
Chemicals
Antibodies, Monoclonal B7-1 Antigen DNA, Viral Epitopes Epitopes, T-Lymphocyte Histocompatibility Antigens Class I Interleukin-2 Ligands Oligonucleotides Peptide Library Peptides Receptors, Antigen, T-Cell Intercellular Adhesion Molecule-1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Crawford Frances
Howard Hughes Medical Institute, Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado, USA.
Huseby Eric
White Janice
Marrack Philippa
Kappler John W
Conflict of Interest

The authors have declared that no conflicts of interest exist.

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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.0020090
Published
2004-04-00
Epub
2004-00-13
Pages
E90
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC387264
Subset
IM
Grants
NIAID NIH HHS · R01 AI018785 · United States
NIAID NIH HHS · AI-17134 · United States
NIAID NIH HHS · AI-18785 · United States
NIAID NIH HHS · R01 AI017134 · United States
NIAID NIH HHS · R37 AI018785 · United States
NIAID NIH HHS · R56 AI017134 · United States
NIAID NIH HHS · AI-22295 · United States
NIAID NIH HHS · R56 AI018785 · United States
NIAID NIH HHS · P01 AI022295 · United States
Databases
GENBANK
AJ278965, AY522575, L22858, X52264
External Links
PubMed source DOI: 10.1371/journal.pbio.0020090 PMC Full Text View journal details
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