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

V. Monsurrò, M. B. Nielsen, A. Perez-Diez, M. E. Dudley, E. Wang, S. A. Rosenberg, F. M. Marincola

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Abstract

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-γ ex vivo and proliferate in vitro. Thus, repeated exposure to immunogenic peptides benefited immune competence. These results provide a rationale for immunization strategies.

Original languageEnglish
Pages (from-to)5817-5825
Number of pages9
JournalJournal of Immunology
Volume166
Issue number9
DOIs
Publication statusPublished - 1 May 2001

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Monsurrò, V., Nielsen, M. B., Perez-Diez, A., Dudley, M. E., Wang, E., Rosenberg, S. A., & Marincola, F. M. (2001). Kinetics of TCR use in response to repeated epitope-specific immunization. Journal of Immunology, 166(9), 5817-5825. https://doi.org/10.4049/jimmunol.166.9.5817