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

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.

Full Text

Duke Authors

Cited Authors

  • Monsurrò, V; Nielsen, MB; Perez-Diez, A; Dudley, ME; Wang, E; Rosenberg, SA; Marincola, FM

Published Date

  • May 1, 2001

Published In

Volume / Issue

  • 166 / 9

Start / End Page

  • 5817 - 5825

PubMed ID

  • 11313426

International Standard Serial Number (ISSN)

  • 0022-1767

Language

  • eng

Conference Location

  • United States