Kinetics of TCR Use in Response to Repeated Epitope-Specific Immunization

• 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.9.5817

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.