Design and use of conditional MHC class I ligands.
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.
Toebes
Mireille
M
Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Coccoris
Miriam
M
Bins
Adriaan
A
Rodenko
Boris
B
Gomez
Raquel
R
Nieuwkoop
Nella J
NJ
van de Kasteele
Willeke
W
Rimmelzwaan
Guus F
GF
Haanen
John B A G
JB
Ovaa
Huib
H
Schumacher
Ton N M
TN
D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics; D066298:In Vitro Techniques; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D015394:Molecular Structure; D046912:Multiprotein Complexes; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010777:Photochemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014466:Ultraviolet Rays
D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D008024:Ligands; D046912:Multiprotein Complexes; D009842:Oligopeptides