Design and use of conditional MHC class I ligands

Nat Med. 2006 Feb;12(2):246-51. doi: 10.1038/nm1360. Epub 2006 Feb 5.


Major histocompatibility complex (MHC) class I molecules associate with a variety of peptide ligands during biosynthesis and present these ligands on the cell surface for recognition by cytotoxic T cells. We have designed conditional MHC ligands that form stable complexes with MHC molecules but degrade on command, by exposure to a defined photostimulus. 'Empty MHC molecules' generated in this manner can be loaded with arrays of peptide ligands to determine MHC binding properties and to monitor antigen-specific T-cell responses in a high-throughput manner. We document the value of this approach by identifying cytotoxic T-cell epitopes within the H5N1 influenza A/Vietnam/1194/04 genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drug Design
  • HLA-A2 Antigen / chemistry
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / metabolism
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / genetics
  • In Vitro Techniques
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / immunology
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Molecular
  • Molecular Structure
  • Multiprotein Complexes
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Photochemistry
  • Spectrometry, Mass, Electrospray Ionization
  • T-Lymphocytes, Cytotoxic / immunology
  • Ultraviolet Rays


  • HLA-A2 Antigen
  • Histocompatibility Antigens Class I
  • Immunodominant Epitopes
  • Ligands
  • Multiprotein Complexes
  • Oligopeptides