Conditional MHC class I ligands and peptide exchange technology for the human MHC gene products HLA-A1, -A3, -A11 and -B7

Arnold H. Bakker, Rieuwert Hoppes, Carsten Linnemann, Mireille Toebes, Boris Rodenko, Celia R. Berkers, Sine Reker Hadrup, Wirn J. E. van Esch, Mirjam H. M. Heemskerk, Huib Ovaa, Ton N. M. Schumacher

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Major histocompatibility complex (MHC) class I multimer technology has become an indispensable immunological assay system to dissect antigen-specific cytotoxic CD8(+) T cell responses by flow cytometry. However, the development of high-throughput assay systems, in which T cell responses against a multitude of epitopes are analyzed, has been precluded by the fact that for each T cell epitope, a separate in vitro MHC refolding reaction is required. We have recently demonstrated that conditional ligands that disintegrate upon exposure to long-wavelength UV light can be designed for the human MHC molecule HLA-A2. To determine whether this peptide-exchange technology can be developed into a generally applicable approach for high throughput MHC based applications we set out to design conditional ligands for the human MHC gene products HLA-A1, -A3, -A11, and -B7. Here, we describe the development and characterization of conditional ligands for this set of human MHC molecules and apply the peptide-exchange technology to identify melanoma-associated peptides that bind to HLA-A3 with high affinity. The conditional ligand technology developed here will allow high-throughput MHC-based analysis of cytotoxic T cell immunity in the vast majority of Western European individuals.
Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number10
Pages (from-to)3825-3830
Number of pages6
ISSN0027-8424
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • Multidisciplinary
  • Genetics
  • CD8
  • Epitope
  • T cell
  • gene product
  • HLA A1 antigen
  • HLA A11 antigen
  • HLA A3 antigen
  • HLA B7 antigen
  • ligand
  • major histocompatibility antigen class 1
  • peptide
  • epitope
  • HLA A antigen
  • HLA antigen class 1
  • HLA-A11
  • unclassified drug
  • analytic method
  • antigen binding
  • article
  • binding affinity
  • cytotoxic T lymphocyte
  • high throughput screening
  • human
  • human cell
  • immunoassay
  • nucleotide sequence
  • priority journal
  • protein binding
  • T lymphocyte
  • technology
  • allele
  • CD8+ T lymphocyte
  • cell clone
  • IC 50
  • immunology
  • kinetics
  • melanoma
  • methodology
  • protein engineering
  • protein folding
  • protein quaternary structure
  • ultraviolet radiation
  • Alleles
  • CD8-Positive T-Lymphocytes
  • Clone Cells
  • Epitopes
  • Histocompatibility Antigens Class I
  • HLA-A Antigens
  • HLA-A1 Antigen
  • HLA-A3 Antigen
  • HLA-B7 Antigen
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Ligands
  • Melanoma
  • Peptides
  • Protein Engineering
  • Protein Folding
  • Protein Structure, Quaternary
  • Ultraviolet Rays
  • LIGANDS
  • HLA-A11 Antigen
  • MULTIDISCIPLINARY
  • T-CELLS
  • ADOPTIVE TRANSFER
  • MOLECULES
  • BINDING
  • EPITOPES
  • IDENTIFICATION
  • LYMPHOCYTES
  • ANTIGEN
  • VITRO
  • IMMUNOTHERAPY
  • immunity
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
  • HLA-A1
  • HLA-A3
  • HLA-B7
  • major histocompatibility complex I ligands
  • melanoma-associated peptides
  • 02506, Cytology - Animal
  • 02508, Cytology - Human
  • 10060, Biochemistry studies - General
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 34502, Immunology - General and methods
  • Chemical Coordination and Homeostasis
  • cytotoxic T cell immune system, blood and lymphatics
  • pepticle-exchange technology laboratory equipment
  • Biochemistry and Molecular Biophysics
  • Immune System
  • Methods and Techniques

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