Peptide-specific CD8+T-cell evolution in vivo: Response to peptide vaccination with Melan-A/MART-I

Item Type:	Article
Title:	Peptide-specific CD8+T-cell evolution in vivo: Response to peptide vaccination with Melan-A/MART-I
Creators Name:	Jaeger, E. and Hoehn, H. and Necker, A. and Foerster, R. and Karbach, J. and Freitag, K. and Neukirch, C. and Castelli, C. and Salter, R.D. and Knuth, A. and Maeurer, M.J.
Abstract:	Monitoring of CD8+ T-cell responses in cancer patients during peptide vaccination is essential to provide useful surrogate markers and to demonstrate vaccine efficacy. We have longitudinally followed CD8+ T-cell responses in 3 melanoma patients who were immunized with peptides derived from Melan-A/MART-I. Recombinant HLA-A2 tetramers loaded with the naturally presented Melan-AJMART-I nonamer peptide (AAGIGILTV) and the Melan-A/MART-I analog (ELAGIGILTV) were used in combination with phenotypical analysis for different T-cell subsets including naive T cells, effector T cells, "true memory" T cells and "memory effector" T cells, based on CD45RA/RO and CCR7-expression. At least in a single patient, T cells binding to the AAGIGILTV epitope were detected in naive, precursor (CD45RA+/CCR7+) CD8+ T cells, and CD8+ T cells binding to the analog ELAGIGILTV peptide were identified in the terminally differentiated (CD45RA+/CCR7-) T-cell subset. Molecular and functional analysis of tetramer-binding T cells revealed that the T-cell receptor (TCR) repertoire was oligo/polyclonal in AAGIGILTV-reactive T cells, but different and restricted to a few TCR clonotypes in ELAGIGILTV-reactive T cells prior to vaccination. The TCR repertoire reactive with Melan-AJMART-I peptide epitopes was broadened during vaccination and exhibited a different profile of cytokine release after specific stimulation: tetramer-binding T cells from 2/3 patients secreted granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-γ but not interleukin-2 (IL-2) in response to Melan-A/MART-I peptides. In the third patient, tetramer-binding T cells secreted IL-2 exclusively. Our results show that T-cell responses to peptide vaccination consist of different T-cell subsets associated with different effector functions. Complementary analysis for TCR CDR3 and cytokine profiles may be useful to define the most effective CD8+ T-cell population induced by peptide vaccination.
Keywords:	Immunotherapy, Melanoma, T Cells, TCR, Vaccination
Source:	International Journal of Cancer
ISSN:	0020-7136
Publisher:	Wiley
Volume:	98
Number:	3
Page Range:	376-388
Date:	1 January 2002
Official Publication:	https://doi.org/10.1002/ijc.10165
PubMed:	View item in PubMed

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