Kinetics of TCR use in response to repeated epitope-specific immunization.
Journal Article (Journal Article)
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; Nielsen, MB; Perez-Diez, A; Dudley, ME; Wang, E; Rosenberg, SA; Marincola, FM
- May 1, 2001
Volume / Issue
- 166 / 9
Start / End Page
- 5817 - 5825
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States