Quantifying and imaging NY-ESO-1/LAGE-1-derived epitopes on tumor cells using high affinity T cell receptors.
Presentation of intracellular tumor-associated Ags (TAAs) in the context of HLA class I molecules offers unique cancer-specific cell surface markers for the identification and targeting of tumor cells. For most peptide Ags, the levels of and variations in cell surface presentation remain unknown, yet these parameters are of crucial importance when considering specific TAAs as targets for anticancer therapy. Here we use a soluble TCR with picomolar affinity for the HLA-A2-restricted 157-165 epitope of the NY-ESO-1 and LAGE-1 TAAs to investigate presentation of this immunodominant epitope on the surface of a variety of cancer cells. By single molecule fluorescence microscopy, we directly visualize HLA-peptide presentation for the first time, demonstrating that NY-ESO-1/LAGE-1-positive tumor cells present 10-50 NY-ESO-1/LAGE-1(157-165) epitopes per cell.
Purbhoo
Marco A
MA
Avidex, Ltd., Abingdon, UK.
Sutton
Deborah H
DH
Brewer
Joanna E
JE
Mullings
Rebecca E
RE
Hill
Maxine E
ME
Mahon
Tara M
TM
Karbach
Julia
J
Jäger
Elke
E
Cameron
Brian J
BJ
Lissin
Nikolai
N
Vyas
Paresh
P
Chen
Ji-Li
JL
Cerundolo
Vincenzo
V
Jakobsen
Bent K
BK
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000096:biosynthesis / Q000378:metabolism; D000954:Antigens, Surface; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000096:biosynthesis / Q000378:metabolism; D045325:HCT116 Cells; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell