Kinetics of TCR use in response to repeated epitope-specific immunization

Selection of T cell-directed immunization strategies is based extensively o n discordant information derived from preclinical models. We characterized the kinetics of T cell selection in response to repeated antigenic challeng e. By enumerating with epitope/HLA tetrameric complexes (tHLA) vaccine-elic ited T cell precursor frequencies (Tc-pf) in melanoma patients exposed to t he modified gp100 epitope gp100:209-217 (g209-2M) we observed in most patie nts that the Tc-pf increased with number of immunizations. One patient's ki netics were further characterized. Dissociation kinetics of g209-2M/tHLA su ggested enrichment of T cell effector populations expressing TCR with progr essively higher affinity. Furthermore, vaccine-elicited T cells maintained the ability to express IFN-gamma ex vivo and proliferate in vitro. Thus, re peated exposure to immunogenic peptides benefited immune competence. These results provide a rationale for immunization strategies.