title: Functional avidity of tumor antigen-specific CTL recognition directly correlates with the stability of MHC/peptide multimer binding to TCR.
abstract: Avidity of Ag recognition by tumor-specific T cells is one of the main parameters that determines the potency of a tumor rejection Ag. In this study we show that the relative efficiency of staining of tumor Ag-specific T lymphocytes with the corresponding fluorescent MHC class I/peptide multimeric complexes can considerably vary with staining conditions and does not necessarily correlate with avidity of Ag recognition. Instead, we found a clear correlation between avidity of Ag recognition and the stability of MHC class I/peptide multimeric complexes interaction with TCR as measured in dissociation kinetic experiments. These findings are relevant for both identification and isolation of tumor-reactive CTL.
authors.affiliation: Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Hôpital Orthopédique, Niveau 5, Avenue Pierre-Decker 4, CH 1005 Lausanne, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dutoit
authors.forename: Verena
authors.initials: V
authors.lastname: Rubio-Godoy
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Doucey
authors.forename: Pascal
authors.initials: P
authors.lastname: Batard
authors.forename: Danielle
authors.initials: D
authors.lastname: Liénard
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Daniel
authors.initials: D
authors.lastname: Speiser
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D013194:Staining and Labeling; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell