Cutting edge: characterization of allorestricted and peptide-selective alloreactive T cells using HLA-tetramer selection.
The vast majority of alloreactive T cells recognize foreign MHC molecules in a peptide-dependent manner. A subpopulation of these peptide-dependent alloreactive T cells is peptide-specific and contains T cells that are of interest for tumor immunotherapy. Allorestricted T cells (i.e., peptide-specific and alloreactive) specific for tumor-associated Ags can be raised in vitro. However, it is technically difficult to distinguish between peptide-specific and peptide-nonspecific alloreactive T cells by functional assays in vitro. Here we show for the first time that allorestricted T cells specifically bind HLA-peptide tetrameric complexes, as nominal Ag-specific T cells would do. In consequence, fluorescent HLA-peptide tetrameric complexes can be used for sorting and cloning of allorestricted CTLs specific for a peptide of interest. We also show by the mean of HLA-peptide tetramers the existence of peptide-selective alloreactive T cells that recognize a conformation on the foreign-MHC brought about by some but not all peptides bound.
Moris
A
A
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.
Teichgräber
V
V
Gauthier
L
L
Bühring
H J
HJ
Rammensee
H G
HG
D002460:Cell Line; D002461:Cell Line, Transformed; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D010446:Peptide Fragments