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The Journal of Immunology, 2001, 166: 5817-5825.
Copyright © 2001 by The American Association of Immunologists

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

Vladia Monsurrò*, Mai-Britt Nielsen{dagger}, Ainhoa Perez-Diez{dagger}, Mark E. Dudley{dagger}, Ena Wang{dagger}, Steven A. Rosenberg{dagger} and Francesco M. Marincola1,*,{dagger}

* HLA Laboratory, Department of Transfusion Medicine, Clinical Center, and {dagger} Surgery Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

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.




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