Kinetics of TCR use in response to repeated epitope-specific immunization.
Selection of T cell-directed immunization strategies is based extensively on discordant information derived from preclinical models. We characterized the kinetics of T cell selection in response to repeated antigenic challenge. By enumerating with epitope/HLA tetrameric complexes (tHLA) vaccine-elicited T cell precursor frequencies (Tc-pf) in melanoma patients exposed to the modified gp100 epitope gp100:209-217 (g209-2M) we observed in most patients that the Tc-pf increased with number of immunizations. One patient's kinetics were further characterized. Dissociation kinetics of g209-2M/tHLA suggested enrichment of T cell effector populations expressing TCR with progressively higher affinity. Furthermore, vaccine-elicited T cells maintained the ability to express IFN-gamma ex vivo and proliferate in vitro. Thus, repeated exposure to immunogenic peptides benefited immune competence. These results provide a rationale for immunization strategies.
Monsurrò
V
V
HLA Laboratory, Department of Transfusion Medicine, Clinical Center, and Surgery Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nielsen
M B
MB
Perez-Diez
A
A
Dudley
M E
ME
Wang
E
E
Rosenberg
S A
SA
Marincola
F M
FM
D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D002999:Clone Cells; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007115:Immunization Schedule; D007700:Kinetics; D008024:Ligands; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008545:Melanoma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C548638:g209-2M melanoma peptide; D058951:gp100 Melanoma Antigen