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-elic...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-05, Vol.166 (9), p.5817-5825
Main Authors: Monsurro, Vladia, Nielsen, Mai-Britt, Perez-Diez, Ainhoa, Dudley, Mark E, Wang, Ena, Rosenberg, Steven A, Marincola, Francesco M
Format: Article
Language:English
Subjects:
Cancer Vaccines - administration & dosage
Cancer Vaccines - immunology
Clone Cells
Dose-Response Relationship, Immunologic
Down-Regulation - immunology
Epitopes, T-Lymphocyte - immunology
Epitopes, T-Lymphocyte - metabolism
gp100 Melanoma Antigen
HLA Antigens - analysis
Humans
Immunization Schedule
Kinetics
Ligands
Lymphocyte Activation
Lymphocyte Count
Melanoma - immunology
Membrane Glycoproteins - administration & dosage
Membrane Glycoproteins - immunology
Neoplasm Proteins - administration & dosage
Neoplasm Proteins - immunology
Peptide Fragments - administration & dosage
Peptide Fragments - immunology
Peptides
Protein Binding - immunology
Receptors, Antigen, T-Cell - metabolism
Stem Cells - immunology
Stem Cells - metabolism
Stem Cells - pathology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
Tumor Cells, Cultured
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.166.9.5817